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Joseph P.They also suggest that the local presence of multiple layers of <a href="https://a.gup.pe/u/immune" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@immune</a> subversion in cancers depends on the individual tissue, <a href="https://a.gup.pe/u/treatment" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@treatment</a> , tumor type, and the difference between primary <a href="https://mstdn.science/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> and metastatic lesion. The authors also found that the results of the <a href="https://a.gup.pe/u/clinicaltrial" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@clinicaltrial</a> were in line with the results of a fully human organotypic tumor <a href="https://mstdn.science/tags/ExplantModel" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ExplantModel</a>, which is a simple model with a straightforward approach.

Joseph P.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 <a href="https://a.gup.pe/u/tissue" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@tissue</a> level. Tumor <a href="https://a.gup.pe/u/cell" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@cell</a> death and a specific pattern of <a href="https://mstdn.science/tags/cytokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cytokine</a> and <a href="https://mstdn.science/tags/chemokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#chemokine</a> modulation are observed in the <a href="https://mstdn.science/tags/ExplantModel" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ExplantModel</a> and in <a href="https://a.gup.pe/u/tumor" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@tumor</a> biopsies from a <a href="https://mstdn.science/tags/ClinicalTrial" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ClinicalTrial</a>. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death.

Joseph P.<a href="https://a.gup.pe/u/explainpaper" class="u-url mention" rel="nofollow noopener noreferrer" target="_blank">@explainpaper</a>Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer PatientsNiels 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 <a href="https://qoto.org/tags/Colorectal" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#Colorectal</a> <a href="https://qoto.org/tags/Cancer" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#Cancer</a> <a href="https://qoto.org/tags/Liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#Liver</a> Metastases<a href="https://qoto.org/tags/Cancer" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#Cancer</a> progression is a process in which cancer cells and <a href="https://qoto.org/tags/immune" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immune</a> cells interact with each other in a way that can lead to the growth and spread of cancer. In <a href="https://qoto.org/tags/colorectal" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#colorectal</a> cancer, when the cancer has spread to other parts of the body, it is called <a href="https://qoto.org/tags/metastasis" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#metastasis</a> and it is very difficult to treat. Treatments such as PD-1/PD-L1 blockade and <a href="https://qoto.org/tags/chemokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#chemokine</a> 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 <a href="https://qoto.org/tags/immunosuppression" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immunosuppression</a> and <a href="https://qoto.org/tags/immune" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immune</a> evasion. In this research paper, the authors studied the microenvironment in <a href="https://qoto.org/tags/CRC" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CRC</a> <a href="https://qoto.org/tags/liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liver</a> metastases and identified a network of <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> 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 <a href="https://qoto.org/tags/liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liver</a> metastases of <a href="https://qoto.org/tags/colorectal" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#colorectal</a> cancer (<a href="https://qoto.org/tags/CRC" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CRC</a>). the environment induces migration of T lymphocytes, which produce a <a href="https://qoto.org/tags/cytokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cytokine</a> called CCL5. This CCL5 then supports tumor growth and spread by influencing macrophages and <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> cells. The environment is immunosuppressive and the tumor cells are exploiting the host's <a href="https://qoto.org/tags/immune" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immune</a> 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 <a href="https://qoto.org/tags/tissue" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tissue</a> level. Tumor <a href="https://qoto.org/tags/cell" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cell</a> death and a specific pattern of <a href="https://qoto.org/tags/cytokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cytokine</a> and <a href="https://qoto.org/tags/chemokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#chemokine</a> modulation are observed in the <a href="https://qoto.org/tags/ExplantModel" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ExplantModel</a> and in <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> biopsies from a <a href="https://qoto.org/tags/ClinicalTrial" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ClinicalTrial</a>. Macrophages are the key for these anti-tumoral effects, as they produce IFNs and reactive oxygen species which cause tumor cell death. <a href="https://qoto.org/tags/CCR5" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CCR5</a> 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 <a href="https://qoto.org/tags/myeloid" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#myeloid</a> 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 <a href="https://qoto.org/tags/immunosuppression" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immunosuppression</a> , <a href="https://qoto.org/tags/angiogenesis" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#angiogenesis</a>, and <a href="https://qoto.org/tags/chemotherapy" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#chemotherapy</a> resistance.The microenvironment of the invasive margin of <a href="https://qoto.org/tags/liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liver</a> metastases. There was no relevant Th1, Th2, or Th17 <a href="https://qoto.org/tags/cytokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cytokine</a> signature present in any of the samples. However, the authors did find that <a href="https://qoto.org/tags/chemokines" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#chemokines</a> and <a href="https://qoto.org/tags/macrophage" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#macrophage</a>-related cytokines were significantly increased at the invasive margin. Chemokines are molecules that help to attract <a href="https://qoto.org/tags/immune" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immune</a> cells to the area, and macrophage-related cytokines are molecules that help to regulate the activity of <a href="https://qoto.org/tags/macrophages" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#macrophages</a>, which are a type of immune cell. 98% of the CD3+ <a href="https://qoto.org/tags/lymphocyte" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#lymphocyte</a> s in the resection specimens were positive for PD-1, which is a molecule that helps to regulate the activity of the immune system.<a href="https://qoto.org/tags/CCL5" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CCL5</a> is a protein produced by T cells, which are a type of white blood cell. <a href="https://qoto.org/tags/CCR5" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CCR5</a> is a receptor found on metastatic tumor cells, which are cancer cells that have spread from the primary <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> to other parts of the body. In this research paper, it was found that CCL5 has <a href="https://qoto.org/tags/pleiotropic" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#pleiotropic</a> tumor-promoting effects on <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> cells and tumor-associated <a href="https://qoto.org/tags/macrophage" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#macrophage</a> s. This means that CCL5 has multiple effects on both the cancer cells and the macrophages, which are a type of white <a href="https://qoto.org/tags/blood" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#blood</a> <a href="https://qoto.org/tags/cell" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cell</a>, that are associated with the <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a>. CCL5 was produced mainly by T cells located at the invasive margin and <a href="https://qoto.org/tags/peritumoral" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#peritumoral</a> stroma of metastases, and that CCR5 was dominantly expressed by metastatic tumor cells. CCL5 also had effects on tumor <a href="https://qoto.org/tags/CellProliferation" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CellProliferation</a>, invasive tumor <a href="https://qoto.org/tags/CellBehavior" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CellBehavior</a>, and increased production of matrix <a href="https://qoto.org/tags/metalloproteinas" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#metalloproteinas</a> es by tumor-associated macrophages. Finally, they found that CCR5 inhibition had an effect on key molecules of <a href="https://qoto.org/tags/epithelial" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#epithelial</a> to <a href="https://qoto.org/tags/mesenchymal" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#mesenchymal</a> transition ( <a href="https://qoto.org/tags/EMT" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#EMT</a> ).The researchers wanted to test the effects of <a href="https://qoto.org/tags/CCR5" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CCR5</a> blockade, which is a way of blocking the CCR5 receptor on cells, using a drug called maraviroc. They used human <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> <a href="https://qoto.org/tags/explantmodel" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#explantmodel</a> s, which are samples of <a href="https://qoto.org/tags/tissue" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tissue</a> from advanced <a href="https://qoto.org/tags/CRC" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CRC</a> patients with <a href="https://qoto.org/tags/liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liver</a> metastases. Maraviroc led to morphologically overt tumor <a href="https://qoto.org/tags/CellDeath" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CellDeath</a> in the <a href="https://qoto.org/tags/explants" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#explants</a>, which means that the tumor cells died and changed in appearance. The researchers then tested the hypothesis that <a href="https://qoto.org/tags/macrophage" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#macrophage</a> s, (type of white blood cell), were required for the tumor cell death-inducing effects of CCR5 blockade. They used clodronate <a href="https://qoto.org/tags/liposome" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liposome</a> s to deplete CD163+ TAMs, ( <a href="https://qoto.org/tags/macrophage" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#macrophage</a> s associated with tumors) and found that combining clodronate with CCR5 inhibition abrogated the immediate tumor cell death-inducing effects of <a href="https://qoto.org/tags/CCR5" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#CCR5</a> inhibition. This confirmed the role of macrophages in this process. IFN-g induced stromal CD163+ <a href="https://qoto.org/tags/macrophage" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#macrophage</a> <a href="https://qoto.org/tags/cell" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cell</a> death and led to a reconfiguration of the <a href="https://qoto.org/tags/myeloid" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#myeloid</a> 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 <a href="https://qoto.org/tags/antibody" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#antibody</a> had similar functional effects to maraviroc.A <a href="https://qoto.org/tags/ClinicalTrial" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ClinicalTrial</a> (MARACON) was conducted to test the effects of a drug called maraviroc on patients with advanced-stage <a href="https://qoto.org/tags/metastatic" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#metastatic</a> colorectal <a href="https://qoto.org/tags/cancer" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cancer</a>. The <a href="https://qoto.org/tags/trial" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#trial</a> 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 <a href="https://qoto.org/tags/microenvironment" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#microenvironment</a> and led to objective clinical responses. These responses included induction of central <a href="https://qoto.org/tags/TumorNecrosis" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#TumorNecrosis</a>, reduction of tumor cell death, and reduction of key <a href="https://qoto.org/tags/cytokine" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cytokine</a> s and growth factors that promote tumor growth. The drug was also found to be very well tolerated, with mild elevation of <a href="https://qoto.org/tags/liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liver</a> 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 <a href="https://qoto.org/tags/therapy" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#therapy</a> used to treat <a href="https://qoto.org/tags/cancer" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#cancer</a>. 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 <a href="https://qoto.org/tags/liver" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#liver</a> metastases, but is a systemic feature. They also suggest that the local presence of multiple layers of <a href="https://qoto.org/tags/immune" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#immune</a> subversion in cancers depends on the individual tissue, <a href="https://qoto.org/tags/treatment" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#treatment</a>, tumor type, and the difference between primary <a href="https://qoto.org/tags/tumor" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#tumor</a> and metastatic lesion. The authors also found that the results of the <a href="https://qoto.org/tags/ClinicalTrial" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ClinicalTrial</a> were in line with the results of a fully human organotypic tumor <a href="https://qoto.org/tags/ExplantModel" class="mention hashtag" rel="nofollow noopener noreferrer" target="_blank">#ExplantModel</a>, 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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