#metastasis — Public Fediverse posts
Live and recent posts from across the Fediverse tagged #metastasis, aggregated by home.social.
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https://www.europesays.com/es/661902/ La acumulación de ácidos biliares impulsa la propagación del cáncer de mama #ácidos #acumulación #biliares #cáncer #derivados #desarrollo #dirigidas #disbiosis #ES #España #especifica #estrategias #Health #impulsa #inducidos #Inflamación #lo #mama #mamario #metabolitos #metastásico #Metástasis #microbioma #promueve #propagación #provocan #reducir #respalda #riesgo #Salud #sistémica #Spain #tejido #tumores
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https://www.europesays.com/es/661713/ La acumulación de ácidos biliares impulsa la propagación del cáncer de mama #ácidos #acumulación #biliares #cáncer #derivados #desarrollo #dirigidas #disbiosis #ES #España #especifica #estrategias #Health #impulsa #inducidos #Inflamación #lo #mama #mamario #metabolitos #metastásico #Metástasis #microbioma #promueve #propagación #provocan #reducir #respalda #riesgo #Salud #sistémica #Spain #tejido #tumores
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https://www.europesays.com/ie/588016/ Bile acid buildup linked to aggressive breast cancer progression #Bile #BreastCancer #cancer #Drugs #Dysbiosis #Éire #Health #Hormone #IE #Ireland #Lungs #medicine #Metabolism #Metastasis #Microbiome #Receptor #Research
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https://www.europesays.com/es/588244/ Las vesículas extracelulares tumorales ofrecen valor pronóstico en el cáncer de pulmón #animal #biomarcadores #cáncer #circulantes #Contenidos #dos #ES #España #extracelulares #Formación #Health #Metástasis #modelo #muerte #ofrecen #Pacientes #predicen #promueven #pronóstico #pulmón #riesgo #Salud #Spain #tumorales #valor #vesículas
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https://www.europesays.com/es/588149/ Apalutamida perfila una nueva vía terapéutica en cáncer de próstata localizado de alto riesgo #alto #apalutamida #aparición #cáncer #cirugía #despues #ES #España #Estudio #frente #Health #hormonal #localizado #mejora #Metástasis #muerte #muestran #nueva #patológica #perfila #prostata #proteus #respuesta #resultados #retrasa #riesgo #Salud #sola #Spain #su #terapéutica #terapia #uso #via
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https://www.europesays.com/es/586768/ Lorlatinib consolida un nuevo horizonte a largo plazo en cáncer de pulmón ALK+ #ALK #anos #cáncer #cerebrales #consolida #control #crizotinib #crown #duradero #ES #España #Estudio #frente #Health #horizonte #largo #lorlatinib #Metástasis #muerte #muestra #nuevo #plazo #progresión #pulmón #reducción #riesgo #Salud #seguimiento #siete #Spain
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https://www.europesays.com/ie/510395/ Implanted collagen tiles double survival for brain metastasis patients #Brachytherapy #Brain #BrainMetastases #BrainSurgery #cancer #ClinicalTrial #Collagen #Éire #Health #IE #Ireland #Metastasis #Neurosurgery #oncology #pH #RadiationTherapy #Surgery #therapy #Tumor
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Small bowel cancer: treatment and risk of metastasis #bowelcancer #cancer #metastasis #bowel
... Continue to: https://youtube.com/shorts/MRuu5Yo-hDw?si=X7Xd9zmU-tLJZPdr -
https://www.europesays.com/at/177716/ GLP-1 in der Onkologie: Hinweise auf weniger Metastasen – aber keine Freigabe für Krebsprävention #Asco #AT #Austria #Cancer #ClinicalTrial #Diabetes #Dpp4 #Gesundheit #GLP1 #Health #Inflammation #Metastasis #ObservationalStudy #Oncology #Österreich
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Stomach cancer: treatment and risk of metastasis #stomach #stomachcancer #metastasis #oncology
... Continue to: https://youtube.com/shorts/Hrj-RjdiQik?si=-e5QkOdh7Ppvzjkw -
Cancer kills most via primary tumor cells seeding distant masses. But bloodstream is hostile to solo CTCs. @[email protected] Wandering tumor cells often cluster, boosting survival to form new tumors, offering novel Rx targets. #medx #meded #cancer #metastasis #CTC
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https://www.europesays.com/es/462834/ Resultados positivos con dacomitinib en el cáncer de pulmón no microcítico #beneficio #cáncer #cerebrales #clínica #dacomitinib #egfr #ES #España #Estudio #frecuentes #habitual #Health #Metástasis #microcítico #Mutaciones #no #Pacientes #positivos #práctica #pulmón #realizado #reporta #resultados #Salud #Spain
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https://www.europesays.com/ie/378634/ Targeting IGF2BP2 improves anti-angiogenic therapy effectiveness in colorectal cancer #Angiogenesis #cancer #Cell #Colorectal #ColorectalCancer #Drugs #Efficacy #Éire #GrowthFactor #IE #Insulin #Ireland #Metastasis #Mortality #Protein #Research #RNA #Technology #therapy #Tumor #Vascular
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https://www.europesays.com/es/415030/ Una innovadora plataforma biotecnológica mejora los resultados de la terapia fotodinámica en modelos de cáncer #biotecnológica #cáncer #ES #España #este #fotodinámica #fotosensibilizador #Health #innovadora #liberacion #mejora #Metástasis #modelos #permite #plataforma #programada #protac #recurrencia #reducen #resistencia #resultados #revierten #Salud #sistema #Spain #terapia
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https://www.europesays.com/es/388396/ Encuentran una vía oculta del sistema linfático clave para una mejor comprensión de la metástasis #abre #avances #cambiar #clave #comprensión #DeLa #dentro #desarrollo #desconocida #directamente #eficaces #encontrado #encuentran #entiende #ES #España #este #Estudio #forma #funcionamiento #ganglios #ha #hallazgo #Health #Investigación #linfático #linfáticos #líquido #mejor #Metástasis #oculta #pasar #puede #puerta #reciente #Salud #sistema #Spain #tratamientos #venas #via
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https://www.europesays.com/ie/326098/ RNA micelles enable targeted chemotherapy without immune toxicity #cancer #Cell #chemotherapy #Colorectal #ColorectalCancer #Drugs #Éire #Gemcitabine #Gene #Health #IE #ImmuneResponse #Ireland #Ligand #Lungs #Metastasis #Molecule #Nanoparticle #Pharmacology #Research #RNA #siRNA #Technology #Therapeutics #therapy #Tumor
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https://www.europesays.com/es/343126/ Un virus oncolítico sensibiliza el colangiocarcinoma a la inmunoterapia #animal #células #colangiocarcinoma #eficacia #ES #España #expresión #Formación #Health #induce #inmunoterapia #Metástasis #modelo #neoantígenos #neoviron #oncolítico #presenta #reduciendo #Salud #sensibiliza #Spain #superior #tumorales #Vacunas #Virus
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https://www.europesays.com/es/328525/ La investigación sobre metástasis cerebral en el CNIO abre la puerta a nuevas estrategias terapéuticas personalizadas #abre #banco #buscan #cáncer #cerebral #clínicos #CNIO #dos #ensayos #ES #España #estrategias #Grupo #han #Health #impulsado #Investigación #lidera #Metástasis #metplatform #muestras #nuevas #personalizadas #plataforma #proliferacion #puerta #renacer #Salud #Spain #terapéuticas #trabajo #tratamientos #vivas #ya
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Final #MathOnco keynote at #SMB2025 @smbmathbiology.bsky.social with Mohit K. Jolly taling about Epithelial to Messenchymal Plasticity (EMP). Great talk and of great importance not just for #metastasis (the context in which it is usually studied) but also #treatmentResistance
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Final #MathOnco keynote at #SMB2025 @smbmathbiology.bsky.social with Mohit K. Jolly taling about Epithelial to Messenchymal Plasticity (EMP). Great talk and of great importance not just for #metastasis (the context in which it is usually studied) but also #treatmentResistance
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Substances that slow down migrating cancer cells could be anti-metastatic drug candidates. In this preprint we describe the first computational model for quantitative analysis of cell migration assays for substance screening. #bayes
#cellmigration #metastasis
https://www.biorxiv.org/content/10.1101/2025.06.12.659342v1 -
"By using time-resolved analyses of scRNA-seq data, we determined the potential transitional trajectories of tumor cells and identified the metastasis-initiating subpopulations"
https://link.springer.com/article/10.1007/s11684-024-1081-7
Reading right now. The identification of cells that initiate #metastasis are of interest, although n=2 paired primary and #BoneMarrow samples may be a bit limited.
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"By using time-resolved analyses of scRNA-seq data, we determined the potential transitional trajectories of tumor cells and identified the metastasis-initiating subpopulations"
https://link.springer.com/article/10.1007/s11684-024-1081-7
Reading right now. The identification of cells that initiate #metastasis are of interest, although n=2 paired primary and #BoneMarrow samples may be a bit limited.
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Non-canonical role of the E3 #ubiquitin ligase FBXO3 in PI3K-induced #BreastCancer #metastasis: FBXO3 binds & protects USP4 from DNPEP-mediated degradation, resulting in Twist1 protein stabilization & increased #tumor metastasis #PLOSBiology https://plos.io/3twkOan
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#Postdoctoral position offered by the #KidsCaN group of Céline Delloye-Bourgeois, titled "Exploring the spatio-temporal dynamics of #Neuroblastoma phenotypes
during #metastasis to the bone marrow"
#JobOpening (pdf): https://www.crcl.fr/app/uploads/2023/07/KidsCaN_postdoc_Modymime.pdf
Group website: https://www.crcl.fr/en/tumor-escape-resistance-immunity-department/kidscan-cancer-neuroscience-and-metastasis-in-pediatric-malignancies/Me and the groups I'm in have an ongoing collaboration with this group in #Lyon, France. Great people to work with, excellent data analyses, #DevelopmentalBiology
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Neurociencia del cáncer: así secuestran los tumores el sistema nervioso para crecer más rápido
Michelle Monje lleva años viendo un patrón sorprendente en sus pacientes con glioblastoma. Una vez extirpado el tumor primario, el cáncer vuelve a aparecer pasado un tiempo en el área que más usaban los pacientes por su trabajo. En el caso de una bailarina clásica, reapareció en la zona del cerebelo que controla el equilibrio.
#Neurociencia #Cerebro #Neurología #EnfermedadesNeurológicas #Astrocitoma #Glioma #Glioblastoma #TumorCerebral #Metástasis #Tumor #Cáncer #Oncología #NeuroOncología #Biomedicina #Salud
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Further presentations on #MYCN binding not just DNA but also RNA, #MKK7 mutations in high risk #neuroblastoma, #BARD1 mutations,
DNA damage repair deficiency incl. enhanced #metastasis.Plus 1 minute pitches for posters, including a #poem. 👌
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https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(23)00021-1
"The key biological features of tumor progression are influenced by the circadian rhythm.
The timing of biopsy collection can be crucial for accurate cancer diagnosis.
The metastatic spread of breast cancer occurs predominantly during the rest phase.
Chronotherapy could lead to more effective disease management in cancer patients."
#reviewPaper #circadianRhythm #metastasis #biopsy #chronotherapy #cancer #diagnosis #treatment
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#Metastatic #cancercells find ways to thrive in harsh environments. #StJude #scientists have new clues about how those #cells succeed and how to potentially stop them. “The overarching goal of our lab is to understand how #metastasis works so that we can eventually target it therapeutically,” says Dr. Myriam Labelle of #Oncology. Learn more. http://bit.ly/3ZUjLvN #StJudeResearch #WomenInScience #WHM
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#Metastatic #cancercells find ways to thrive in harsh environments. #StJude #scientists have new clues about how those #cells succeed and how to potentially stop them. “The overarching goal of our lab is to understand how #metastasis works so that we can eventually target it therapeutically,” says Dr. Myriam Labelle of #Oncology. Learn more. http://bit.ly/3ZUjLvN #StJudeResearch #WomenInScience #WHM
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#Metastatic #cancercells find ways to thrive in harsh environments. #StJude #scientists have new clues about how those #cells succeed and how to potentially stop them. “The overarching goal of our lab is to understand how #metastasis works so that we can eventually target it therapeutically,” says Dr. Myriam Labelle of #Oncology. Learn more. http://bit.ly/3ZUjLvN #StJudeResearch #WomenInScience #WHM
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#Metastatic #cancercells find ways to thrive in harsh environments. #StJude #scientists have new clues about how those #cells succeed and how to potentially stop them. “The overarching goal of our lab is to understand how #metastasis works so that we can eventually target it therapeutically,” says Dr. Myriam Labelle of #Oncology. Learn more. http://bit.ly/3ZUjLvN #StJudeResearch #WomenInScience #WHM
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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 JaegerTargeting 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.
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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 JaegerTargeting 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.
-
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 JaegerTargeting 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.
