#macrophages — Public Fediverse posts

UCLA Researchers Identify and Clear Senescent Macrophages to Reverse Fatty Liver Disease in Mice

📰 Original title: Scientists remove “zombie” cells and reverse liver damage in mice

🤖 IA: It's clickbait ⚠️
👥 Usuarios: It's clickbait ⚠️

View full AI summary: https://killbait.com/en/ucla-researchers-identify-and-clear-senescent-macrophages-to-reverse-fatty-liver-disease-in-mice/?redirpost=be87fc0c-de2a-4d1b-a6de-0cc7857a6426

#health #senescentcells #fattyliverdisease #macrophages

#Macrophages don’t just follow chemoattractants to locate sites of infection, they can also create and sculpt them as guidance cues but the mechanisms remain unclear. @robinsall &co show that macrophages extract directional information from their environment from a constant concentration of C5a #chemoattractant, self-generate a gradient & enhance guidance @PLOSBiology https://plos.io/4txkZez

#Macrophages do not possess inherent long-term memory but instead rely on constant stimulation from residual interferon-gamma molecules sequestered on their surface to maintain a primed state against repeat infections.
#Immunology #Genetics #sflorg
https://www.sflorg.com/2026/02/imgy02182601.html

Within tumors in the human body, there are #immune #cells ( #macrophages ) capable of fighting cancer,
but they have been unable to perform their roles properly due to suppression by the tumor.

KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly ⚠️converts immune cells inside tumors into anticancer cell therapies.

KAIST President Kwang Hyung Lee announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which,
when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR
(a #cancer-#recognizing device) proteins on their own...
and are converted into anticancer immune cells known as "#CAR-#macrophages."

❌Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function.

As a result, the effectiveness of existing immune cell therapies has been limited.

✅ CAR-macrophages,
which have recently attracted attention as a next-generation immunotherapy,
have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.

⛔️However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient's blood, followed by cell culture and genetic modification.

This process is time-consuming, costly, and has limited feasibility for
real-world patient applications.

To address this challenge, the research team focused on "#tumor-#associated #macrophages" that are already accumulated around tumors.

⭐️They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles
—designed to be readily absorbed by macrophages
—with both mRNA encoding
cancer-recognition information
and an immunostimulant that activates immune responses.

In other words, in this study,
CAR-macrophages were created by
👉"directly converting the body's own macrophages into anticancer cell therapies inside the body."
https://www.news-medical.net/news/20260102/New-therapeutic-approach-converts-immune-cells-inside-tumors-into-anticancer-cell-therapies.aspx

Within tumors in the human body, there are #immune #cells ( #macrophages ) capable of fighting cancer,
but they have been unable to perform their roles properly due to suppression by the tumor.

KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly ⚠️converts immune cells inside tumors into anticancer cell therapies.

KAIST President Kwang Hyung Lee announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which,
when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR
(a #cancer-#recognizing device) proteins on their own...
and are converted into anticancer immune cells known as "#CAR-#macrophages."

❌Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function.

As a result, the effectiveness of existing immune cell therapies has been limited.

✅ CAR-macrophages,
which have recently attracted attention as a next-generation immunotherapy,
have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.

⛔️However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient's blood, followed by cell culture and genetic modification.

This process is time-consuming, costly, and has limited feasibility for
real-world patient applications.

To address this challenge, the research team focused on "#tumor-#associated #macrophages" that are already accumulated around tumors.

⭐️They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles
—designed to be readily absorbed by macrophages
—with both mRNA encoding
cancer-recognition information
and an immunostimulant that activates immune responses.

In other words, in this study,
CAR-macrophages were created by
👉"directly converting the body's own macrophages into anticancer cell therapies inside the body."
https://www.news-medical.net/news/20260102/New-therapeutic-approach-converts-immune-cells-inside-tumors-into-anticancer-cell-therapies.aspx

Within tumors in the human body, there are #immune #cells ( #macrophages ) capable of fighting cancer,
but they have been unable to perform their roles properly due to suppression by the tumor.

KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly ⚠️converts immune cells inside tumors into anticancer cell therapies.

KAIST President Kwang Hyung Lee announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which,
when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR
(a #cancer-#recognizing device) proteins on their own...
and are converted into anticancer immune cells known as "#CAR-#macrophages."

❌Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function.

As a result, the effectiveness of existing immune cell therapies has been limited.

✅ CAR-macrophages,
which have recently attracted attention as a next-generation immunotherapy,
have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.

⛔️However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient's blood, followed by cell culture and genetic modification.

This process is time-consuming, costly, and has limited feasibility for
real-world patient applications.

To address this challenge, the research team focused on "#tumor-#associated #macrophages" that are already accumulated around tumors.

⭐️They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles
—designed to be readily absorbed by macrophages
—with both mRNA encoding
cancer-recognition information
and an immunostimulant that activates immune responses.

In other words, in this study,
CAR-macrophages were created by
👉"directly converting the body's own macrophages into anticancer cell therapies inside the body."
https://www.news-medical.net/news/20260102/New-therapeutic-approach-converts-immune-cells-inside-tumors-into-anticancer-cell-therapies.aspx

Within tumors in the human body, there are #immune #cells ( #macrophages ) capable of fighting cancer,
but they have been unable to perform their roles properly due to suppression by the tumor.

KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly ⚠️converts immune cells inside tumors into anticancer cell therapies.

KAIST President Kwang Hyung Lee announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which,
when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR
(a #cancer-#recognizing device) proteins on their own...
and are converted into anticancer immune cells known as "#CAR-#macrophages."

❌Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function.

As a result, the effectiveness of existing immune cell therapies has been limited.

✅ CAR-macrophages,
which have recently attracted attention as a next-generation immunotherapy,
have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.

⛔️However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient's blood, followed by cell culture and genetic modification.

This process is time-consuming, costly, and has limited feasibility for
real-world patient applications.

To address this challenge, the research team focused on "#tumor-#associated #macrophages" that are already accumulated around tumors.

⭐️They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles
—designed to be readily absorbed by macrophages
—with both mRNA encoding
cancer-recognition information
and an immunostimulant that activates immune responses.

In other words, in this study,
CAR-macrophages were created by
👉"directly converting the body's own macrophages into anticancer cell therapies inside the body."
https://www.news-medical.net/news/20260102/New-therapeutic-approach-converts-immune-cells-inside-tumors-into-anticancer-cell-therapies.aspx

Within tumors in the human body, there are #immune #cells ( #macrophages ) capable of fighting cancer,
but they have been unable to perform their roles properly due to suppression by the tumor.

KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly ⚠️converts immune cells inside tumors into anticancer cell therapies.

KAIST President Kwang Hyung Lee announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which,
when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR
(a #cancer-#recognizing device) proteins on their own...
and are converted into anticancer immune cells known as "#CAR-#macrophages."

❌Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function.

As a result, the effectiveness of existing immune cell therapies has been limited.

✅ CAR-macrophages,
which have recently attracted attention as a next-generation immunotherapy,
have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.

⛔️However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient's blood, followed by cell culture and genetic modification.

This process is time-consuming, costly, and has limited feasibility for
real-world patient applications.

To address this challenge, the research team focused on "#tumor-#associated #macrophages" that are already accumulated around tumors.

⭐️They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles
—designed to be readily absorbed by macrophages
—with both mRNA encoding
cancer-recognition information
and an immunostimulant that activates immune responses.

In other words, in this study,
CAR-macrophages were created by
👉"directly converting the body's own macrophages into anticancer cell therapies inside the body."
https://www.news-medical.net/news/20260102/New-therapeutic-approach-converts-immune-cells-inside-tumors-into-anticancer-cell-therapies.aspx

https://www.europesays.com/ie/183575/ A Crucial Genetic Mutation Behind Crohn’s Disease Has Finally Been Revealed #Crohn'sDisease #Éire #IE #ImmuneCells #InflammatoryBowelDisease #Ireland #macrophages #Science

#Immune systems of female and male mice age differently, study on #macrophages shows. Explains a mechanism of "inflammaging": survival of #inflammatory cells. https://www.nature.com/articles/d41586-025-02788-0

@roylelab Nice work! This reminds me of a paper published while I was in my PhD lab addressing ER membrane contribution to the Phagocytic cup.

It still stands as a fantastic example of structured hypothesis testing.

https://doi.org/10.1016/j.cell.2005.08.018

#EndoplasmicReticulum #Phagocytosis #macrophages #ScienceMastodon

Another experimental anti-tumor therapy based on weaponized immune cells: #macrophages loaded with drugs attack #glioblastoma cells and activate #immune system.
https://www.science.org/doi/10.1126/scitranslmed.adr4058

#Macrophages are #immune cells good at hoovering up pathogens. Turns out that they are real predators that use gobbled bacteria as fuel. Depending on whether this food is dead or alive they become more tame or go berserk. Massive work. https://www.nature.com/articles/s41586-025-08629-4

Human aging is assoc. with inflammation and intestinal barrier dysfunction. One might assume that barrier permeability would spark increased inflammation. This (and prev.) work suggests the opposite—that #inflammaging, driven by #monocytes and #macrophages appear to *cause* the barrier dysfunction!

How do #apoptotic cells signal to their neighbors to stimulate proliferation? This study shows that apoptotic #ExtracellularVesicles (#EVs) carrying MIF stimulate epithelial #StemCell repopulation, guiding #macrophages to induce proliferation #PLOSBiology https://plos.io/48SeCd3

#Tuberculosis bacteria release tuberculosinyladenosine to help them survive in human #macrophages. This study identifies >100 such #terpene #nucleoside metabolites, revealing how #TB's ancestors acquired the genes to make these lipids #PLOSBiology https://plos.io/4gIfmol

Ezrin, radixin, and moesin are dispensable for macrophage migration and cellular cortex mechanics

#RefereedPreprint c/o @ReviewCommons by Véronique Le Cabec, Sébastien Carréno, Renaud Poincloux and colleagues shows that #macrophages do not require the ERM family proteins for phagocytosis and cell migration, suggesting divergence of macrophage cortical properties

https://www.embopress.org/doi/full/10.1038/s44318-024-00173-7

Superbug that now kills 300,000 people a year evolved rapidly from common bacteria | The Independent
https://www.independent.co.uk/news/science/superbug-antibiotic-resistance-origin-spread-b2575769.html

#Superbug
#CommmonBacteria
#Bacteria
#Evolution
#CysticFibrosis
#PseudomonasAeruginosa
#LungDamage
#Smoking
#Macrophages
#DenselyPopulatedAreas

PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap. https://doi.org/10.1186/s12931-024-02790-6 #Aco #Asthma #Copd #Macrophages #Senescence

New drug against #Tuberculosis: @alexe_mre @TailleuxLudovic &co identify an #oxadiazole-based compound that induces #zinc redistribution in host cells, synergizing with other anti-#TB drugs to control infection in human #macrophages & mice #PLOSBiology https://plos.io/3w60MVs

#StanfordMedicine study flags unexpected cells in lung as suspected source of severe #COVID | https://med.stanford.edu/news/all-news/2024/04/covid-lung-cells.html “Important covid clues! Researchers find that #macrophages - the cells that usually scavenge and destroy viruses - are the cells most susceptible to being infected/hijacked by #SARSCoV2. To enter macrophages, SARS-CoV-2 uses #CD209 receptors (not #ACE2). Interfering with SARS-CoV-2/CD209 binding could be a promising target for new and better prevention and/or treatment!”

COVID-19: Severe lung infection affects heart through “cardiac macrophage shift” 
It is known that COVID-19 increases the risk of heart attack, stroke, and Long COVID but what was not known is whether the damage occurs because the...........
#CardiacFunction #COVID19 #HeartDiseases #LongCOVID #macrophages
SCIEU Team

https://www.scientificeuropean.co.uk/covid-19/covid-19-severe-lung-infection-affects-heart-through-cardiac-macrophage-shift/

Our #immune system constantly fights emerging #cancer cells that arise from mutations. This process is controlled, among other things, by different types of #macrophages. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the #tumor microenvironment.
#Biology #Medical #sflorg
https://www.sflorg.com/2024/02/med02272401.html

EU funding for pioneering research on the treatment of #gliomas: Establishing direct light therapy to combat #brain tumors / @EUeic supports international collaboration with EUR 2.2 million in its #EICPathfinder program / #GliomaTreatment #macrophages
https://nachrichten.idw-online.de/2024/01/17/eu-funding-for-pioneering-research-on-the-treatment-of-glioma

Macrophages are essential immune cells that reside in all tissues. Some macrophages arise from monocytes in the blood, but during fetal development they also come from a unique pathway!

We still have a lot to learn, but here I'll describe how Zhao et al. (2023) used mouse models to uncover hints about which progenitor cells create tissue-macrophages.

https://doi.org/10.1016/j.celrep.2023.113364

#Macrophages #MouseModel #Immunology #Immunity #scRNAseq #FlowCytometry #Research #JournalArticle #JournalClub

1/9🧵

Does #circadian gene expression affect #reprogramming of differentiated cells? Study shows that contaminating #macrophages in #fibroblast culture can inhibit reprogramming to #neurons & #iPSCs, controlled by the clock gene Per1 #PLOSBiology https://plos.io/47YBh6d

How does signaling via extracellular #nucleotides contribute to innate immunity? Systematic #P2Y receptor survey in human #macrophages shows some control #inflammatory #cytokines, others viral replication, and #P2Y11 uniquely combining both roles

Line Lykke Andersen et al Andreas Pichlmair

https://www.embopress.org/doi/full/10.15252/embj.2022113279

Gizmodo: An Existing Drug for Multiple Sclerosis Might Be Useful for Alzheimer's Too, Study Finds https://gizmodo.com/ms-ponesimod-might-be-useful-alzheimers-therapy-study-1850803952?utm_source=regular #insulindegradingenzyme #healthmedicalpharma #neuroinflammation #alzheimersdisease #amyloidplaques #amyloidosis #amyloidbeta #macrophages #glialcells #microglia #zhihuizhu #trem2

Fascinating to see #trainedimmunity used to condition immunomodulatory responses.

I guess it's about inducing the right #epigenetic programme, and then the functional effect can be anything.
#immunology #macrophages @JExpMed #tolerance #immunmodulation #science
https://rupress.org/jem/article/220/11/e20221388/276204/Trained-immunity-of-alveolar-macrophages-enhances?guestAccessKey=6d53512f-5c93-4720-8180-9180f44cda67&utm_source=NewJournalContent%27&%27utm_campaign%27=%27JEM%27&%27utm_medium%27=%27Email&nbd=28080031447&nbd_source=campaigner&_ccCt=g843-2q1v95-cqesgb-cwe4ixj4

"NB cells signal to the BM microenvironment, rewiring via macrophage migration inhibitory factor and #midkine signaling specifically #monocytes ..."

#Neuroblastoma paper by Fetahu et al., the latest publication from the Taschner-Mandl lab in Vienna.

Going through this right now - very alike our own work - and talking to a few team members on Wednesday while they visit our center.

#macrophages #scATACseq #scRNAseq #OpenAccess #cancer #immunology

Data available on EGA, behind a DAC.

#Tumor #cells won’t show their true selves in a #petri dish, isolated from other cells. Rice University researchers developed an upgraded tumor model that houses #osteosarcoma cells beside #immune cells known as #macrophages inside a three-dimensional structure #engineered to mimic #bone.
#Cancer #Engineering #Biology #sflorg
https://www.sflorg.com/2023/03/eng03202301.html

#Innate and #Adaptive #Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms
#COVID19 #Bcells #neutrophils #dendritic_cells #Tcells #NKcells #monocytes #macrophages #SARSCoV2
https://www.mdpi.com/2076-393X/11/2/408

In the middle of an excellent seminar in which Matthias Gromeier presented work on Cancer Immunotherapy with Recombinant Poliovirus, the Zoom session was ended and no luck from the organization's side to restart. 😭

The first 10-15min showed work linking back to original work and ideas from Albert Sabin and David Bodian. Specific targeting of #DendriticCells and #Macrophages, #interferon response.

Hopefully they recorded the seminar.

#cancer #immunotherapy

Are you interested in Immunology and do you want to come to Germany?
1 year Marie Curie Fellowship for a Predoctoral Researcher @[email protected]
#macrophages #Tregs #FlowCytometry Please RT
See details
👇 👇 👇
https://euraxess.ec.europa.eu/jobs/59357

Did you know that dying #cancer cells in solid #tumors can drive tumor-associated #macrophages (TAMs) in both directions? They can become pro-tumorigenic and anti-tumorigenic.

Here is a very nice review article about the interface of TAMs with dying cancer cells in #immunooncology by the lab of Abhishek D. Garg at KU Leuven: https://www.mdpi.com/2073-4409/11/23/3890

#celldeath #efferocytosis #microenvironment #immunosuppression #chemotherapy #radiotherapy

Dear people interested in #organoids #Tcells #Macrophages #Bcells #DendriticCells #MucosalImmunology #microbiome #OrganOnChip #MicroPhysiologicalSystems #IBD #CeliacDisease #iPSCs,

where are you? I want to follow you!

Best regards,
Me

Latest publication from when I was working at the UMC Utrecht: https://www.nature.com/articles/s44161-022-00171-0

Bulk #RNAseq of advanced carotid plaques from 654 patients. This data yielded five plaque types that correlate with clinical representation. And add an additional layer of information on top of the standard #histology.

Also #scRNAseq #GWAS #macrophages #SMC

#atherosclerosis #CoronaryArteryDisease (CAD)

@explainpaper

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients

Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona,Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel,
Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, and Dirk Jaeger

Targeting Tumor-Promoting Microenvironment Through CCR5 Blockade in #Colorectal #Cancer #Liver Metastases

#Cancer progression is a process in which cancer cells and #immune cells interact with each other in a way that can lead to the growth and spread of cancer. In #colorectal cancer, when the cancer has spread to other parts of the body, it is called #metastasis and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and #chemokine modulation have been successful in modifying the interactions between the immune system and cancer, leading to the rejection or suppression of progression. Cancer cells can also alter the immune microenvironment, leading to #immunosuppression and #immune evasion. In this research paper, the authors studied the microenvironment in #CRC #liver metastases and identified a network of #tumor cells and immune cells that exploit the CCL5-CCR5 axis. They then investigated and characterized the effects of blocking the CCL5-CCR5 axis.

the microenvironment of #liver metastases of #colorectal cancer (#CRC).

the environment induces migration of T lymphocytes, which produce a #cytokine called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and #tumor cells. The environment is immunosuppressive and the tumor cells are exploiting the host's #immune cells to their advantage. In other words, the tumor cells are using the host's immune cells to help them grow and spread.

the effects of CCR5 blockade on the #tissue level.

Tumor #cell death and a specific pattern of #cytokine and #chemokine modulation are observed in the #ExplantModel and in #tumor biopsies from a #ClinicalTrial. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. #CCR5 blockade induces a phenotypic shift in the macrophages, which is referred to as a switch from an M2 to an M1 phenotype. This repolarization also reduces levels of CD163+ cells, reshaping the #myeloid cell composition in the microenvironment. The influx of new effector cells due to CCR5 inhibition can shift the effects of CCL5 towards beneficial effects, such as reduction of #immunosuppression , #angiogenesis, and #chemotherapy resistance.

The microenvironment of the invasive margin of #liver metastases.

There was no relevant Th1, Th2, or Th17 #cytokine signature present in any of the samples. However, the authors did find that #chemokines and #macrophage-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract #immune cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of #macrophages, which are a type of immune cell. 98% of the CD3+ #lymphocyte s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.

#CCL5 is a protein produced by T cells, which are a type of white blood cell. #CCR5 is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary #tumor to other parts of the body. In this research paper, it was found that CCL5 has #pleiotropic tumor-promoting effects on #tumor cells and tumor-associated #macrophage s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white #blood #cell, that are associated with the #tumor. CCL5 was produced mainly by T cells located at the invasive margin and #peritumoral stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor #CellProliferation, invasive tumor #CellBehavior, and increased production of matrix #metalloproteinas es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of #epithelial to #mesenchymal transition ( #EMT ).

The researchers wanted to test the effects of #CCR5 blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human #tumor #explantmodel s, which are samples of #tissue from advanced #CRC patients with #liver metastases. Maraviroc led to morphologically overt tumor #CellDeath in the #explants, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that #macrophage s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate #liposome s to deplete CD163+ TAMs, ( #macrophage s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of #CCR5 inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ #macrophage #cell death and led to a reconfiguration of the #myeloid cell compartment. Inhibition of macrophage-derived reactive oxygen species could partially block the anti-tumoral effects of CCR5 inhibition. Finally, they tested the effects of CCL5/CCR5 inhibition and found that both a CCL5 neutralizing antibody and a CCR5 blocking #antibody had similar functional effects to maraviroc.

A #ClinicalTrial (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage #metastatic colorectal #cancer. The #trial involved taking biopsies of the patients before and after treatment with maraviroc, and the results showed that the drug had beneficial effects on the tumor-promoting #microenvironment and led to objective clinical responses. These responses included induction of central #TumorNecrosis, reduction of tumor cell death, and reduction of key #cytokine s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of #liver enzymes being the most common side effect. Finally, the trial showed that partial responses were achieved in patients with previously refractory disease.

CCR5 blockade, is a type of #therapy used to treat #cancer.

The MARACON clinical trial, showed that CCR5 blockade had a positive effect on the tumor microenvironment and led to a higher response rate in subsequent chemotherapies. The authors suggest that this effect is not limited to the #liver metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of #immune subversion in cancers depends on the individual tissue, #treatment, tumor type, and the difference between primary #tumor and metastatic lesion. The authors also found that the results of the #ClinicalTrial were in line with the results of a fully human organotypic tumor #ExplantModel, which is a simple model with a straightforward approach. The authors also note that the survival data from the trial is not conclusive due to the limited number of patients, but that the objective treatment responses are very encouraging. They suggest that CCR5 blockade may be a promising approach and needs to be evaluated further scientifically and clinically.

@explainpaper

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients

Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona,Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel,
Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, and Dirk Jaeger

Targeting Tumor-Promoting Microenvironment Through CCR5 Blockade in #Colorectal #Cancer #Liver Metastases

#Cancer progression is a process in which cancer cells and #immune cells interact with each other in a way that can lead to the growth and spread of cancer. In #colorectal cancer, when the cancer has spread to other parts of the body, it is called #metastasis and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and #chemokine modulation have been successful in modifying the interactions between the immune system and cancer, leading to the rejection or suppression of progression. Cancer cells can also alter the immune microenvironment, leading to #immunosuppression and #immune evasion. In this research paper, the authors studied the microenvironment in #CRC #liver metastases and identified a network of #tumor cells and immune cells that exploit the CCL5-CCR5 axis. They then investigated and characterized the effects of blocking the CCL5-CCR5 axis.

the microenvironment of #liver metastases of #colorectal cancer (#CRC).

the environment induces migration of T lymphocytes, which produce a #cytokine called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and #tumor cells. The environment is immunosuppressive and the tumor cells are exploiting the host's #immune cells to their advantage. In other words, the tumor cells are using the host's immune cells to help them grow and spread.

the effects of CCR5 blockade on the #tissue level.

Tumor #cell death and a specific pattern of #cytokine and #chemokine modulation are observed in the #ExplantModel and in #tumor biopsies from a #ClinicalTrial. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. #CCR5 blockade induces a phenotypic shift in the macrophages, which is referred to as a switch from an M2 to an M1 phenotype. This repolarization also reduces levels of CD163+ cells, reshaping the #myeloid cell composition in the microenvironment. The influx of new effector cells due to CCR5 inhibition can shift the effects of CCL5 towards beneficial effects, such as reduction of #immunosuppression , #angiogenesis, and #chemotherapy resistance.

The microenvironment of the invasive margin of #liver metastases.

There was no relevant Th1, Th2, or Th17 #cytokine signature present in any of the samples. However, the authors did find that #chemokines and #macrophage-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract #immune cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of #macrophages, which are a type of immune cell. 98% of the CD3+ #lymphocyte s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.

#CCL5 is a protein produced by T cells, which are a type of white blood cell. #CCR5 is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary #tumor to other parts of the body. In this research paper, it was found that CCL5 has #pleiotropic tumor-promoting effects on #tumor cells and tumor-associated #macrophage s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white #blood #cell, that are associated with the #tumor. CCL5 was produced mainly by T cells located at the invasive margin and #peritumoral stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor #CellProliferation, invasive tumor #CellBehavior, and increased production of matrix #metalloproteinas es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of #epithelial to #mesenchymal transition ( #EMT ).

The researchers wanted to test the effects of #CCR5 blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human #tumor #explantmodel s, which are samples of #tissue from advanced #CRC patients with #liver metastases. Maraviroc led to morphologically overt tumor #CellDeath in the #explants, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that #macrophage s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate #liposome s to deplete CD163+ TAMs, ( #macrophage s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of #CCR5 inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ #macrophage #cell death and led to a reconfiguration of the #myeloid cell compartment. Inhibition of macrophage-derived reactive oxygen species could partially block the anti-tumoral effects of CCR5 inhibition. Finally, they tested the effects of CCL5/CCR5 inhibition and found that both a CCL5 neutralizing antibody and a CCR5 blocking #antibody had similar functional effects to maraviroc.

A #ClinicalTrial (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage #metastatic colorectal #cancer. The #trial involved taking biopsies of the patients before and after treatment with maraviroc, and the results showed that the drug had beneficial effects on the tumor-promoting #microenvironment and led to objective clinical responses. These responses included induction of central #TumorNecrosis, reduction of tumor cell death, and reduction of key #cytokine s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of #liver enzymes being the most common side effect. Finally, the trial showed that partial responses were achieved in patients with previously refractory disease.

CCR5 blockade, is a type of #therapy used to treat #cancer.

The MARACON clinical trial, showed that CCR5 blockade had a positive effect on the tumor microenvironment and led to a higher response rate in subsequent chemotherapies. The authors suggest that this effect is not limited to the #liver metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of #immune subversion in cancers depends on the individual tissue, #treatment, tumor type, and the difference between primary #tumor and metastatic lesion. The authors also found that the results of the #ClinicalTrial were in line with the results of a fully human organotypic tumor #ExplantModel, which is a simple model with a straightforward approach. The authors also note that the survival data from the trial is not conclusive due to the limited number of patients, but that the objective treatment responses are very encouraging. They suggest that CCR5 blockade may be a promising approach and needs to be evaluated further scientifically and clinically.

@explainpaper

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients

Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona,Thomas Suetterlin, Karsten Brand, Juergen Krauss, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Moritz Koch, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel,
Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Niels Grabe, Christine S. Falk, and Dirk Jaeger

Targeting Tumor-Promoting Microenvironment Through CCR5 Blockade in #Colorectal #Cancer #Liver Metastases

#Cancer progression is a process in which cancer cells and #immune cells interact with each other in a way that can lead to the growth and spread of cancer. In #colorectal cancer, when the cancer has spread to other parts of the body, it is called #metastasis and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and #chemokine modulation have been successful in modifying the interactions between the immune system and cancer, leading to the rejection or suppression of progression. Cancer cells can also alter the immune microenvironment, leading to #immunosuppression and #immune evasion. In this research paper, the authors studied the microenvironment in #CRC #liver metastases and identified a network of #tumor cells and immune cells that exploit the CCL5-CCR5 axis. They then investigated and characterized the effects of blocking the CCL5-CCR5 axis.

the microenvironment of #liver metastases of #colorectal cancer (#CRC).

the environment induces migration of T lymphocytes, which produce a #cytokine called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and #tumor cells. The environment is immunosuppressive and the tumor cells are exploiting the host's #immune cells to their advantage. In other words, the tumor cells are using the host's immune cells to help them grow and spread.

the effects of CCR5 blockade on the #tissue level.

Tumor #cell death and a specific pattern of #cytokine and #chemokine modulation are observed in the #ExplantModel and in #tumor biopsies from a #ClinicalTrial. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. #CCR5 blockade induces a phenotypic shift in the macrophages, which is referred to as a switch from an M2 to an M1 phenotype. This repolarization also reduces levels of CD163+ cells, reshaping the #myeloid cell composition in the microenvironment. The influx of new effector cells due to CCR5 inhibition can shift the effects of CCL5 towards beneficial effects, such as reduction of #immunosuppression , #angiogenesis, and #chemotherapy resistance.

The microenvironment of the invasive margin of #liver metastases.

There was no relevant Th1, Th2, or Th17 #cytokine signature present in any of the samples. However, the authors did find that #chemokines and #macrophage-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract #immune cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of #macrophages, which are a type of immune cell. 98% of the CD3+ #lymphocyte s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.

#CCL5 is a protein produced by T cells, which are a type of white blood cell. #CCR5 is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary #tumor to other parts of the body. In this research paper, it was found that CCL5 has #pleiotropic tumor-promoting effects on #tumor cells and tumor-associated #macrophage s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white #blood #cell, that are associated with the #tumor. CCL5 was produced mainly by T cells located at the invasive margin and #peritumoral stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor #CellProliferation, invasive tumor #CellBehavior, and increased production of matrix #metalloproteinas es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of #epithelial to #mesenchymal transition ( #EMT ).

The researchers wanted to test the effects of #CCR5 blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human #tumor #explantmodel s, which are samples of #tissue from advanced #CRC patients with #liver metastases. Maraviroc led to morphologically overt tumor #CellDeath in the #explants, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that #macrophage s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate #liposome s to deplete CD163+ TAMs, ( #macrophage s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of #CCR5 inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ #macrophage #cell death and led to a reconfiguration of the #myeloid cell compartment. Inhibition of macrophage-derived reactive oxygen species could partially block the anti-tumoral effects of CCR5 inhibition. Finally, they tested the effects of CCL5/CCR5 inhibition and found that both a CCL5 neutralizing antibody and a CCR5 blocking #antibody had similar functional effects to maraviroc.

A #ClinicalTrial (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage #metastatic colorectal #cancer. The #trial involved taking biopsies of the patients before and after treatment with maraviroc, and the results showed that the drug had beneficial effects on the tumor-promoting #microenvironment and led to objective clinical responses. These responses included induction of central #TumorNecrosis, reduction of tumor cell death, and reduction of key #cytokine s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of #liver enzymes being the most common side effect. Finally, the trial showed that partial responses were achieved in patients with previously refractory disease.

CCR5 blockade, is a type of #therapy used to treat #cancer.

The MARACON clinical trial, showed that CCR5 blockade had a positive effect on the tumor microenvironment and led to a higher response rate in subsequent chemotherapies. The authors suggest that this effect is not limited to the #liver metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of #immune subversion in cancers depends on the individual tissue, #treatment, tumor type, and the difference between primary #tumor and metastatic lesion. The authors also found that the results of the #ClinicalTrial were in line with the results of a fully human organotypic tumor #ExplantModel, which is a simple model with a straightforward approach. The authors also note that the survival data from the trial is not conclusive due to the limited number of patients, but that the objective treatment responses are very encouraging. They suggest that CCR5 blockade may be a promising approach and needs to be evaluated further scientifically and clinically.

#SyntheticBiology #tumors #CART #TRUCKs #ICTs #iPSCs #macrophages #TCells #NKCells #bioengineering #CancerVaccine

#SyntheticBiology #tumors #CART #TRUCKs #ICTs #iPSCs #macrophages #TCells #NKCells #bioengineering #CancerVaccine

#SyntheticBiology #tumors #CART #TRUCKs #ICTs #iPSCs #macrophages #TCells #NKCells #bioengineering #CancerVaccine

#SyntheticBiology #tumors #CART #TRUCKs #ICTs #iPSCs #macrophages #TCells #NKCells #bioengineering #CancerVaccine

#SyntheticBiology #tumors #CART #TRUCKs #ICTs #iPSCs #macrophages #TCells #NKCells #bioengineering #CancerVaccine