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Posted On: 09/23/2025 10:10:00 AM
Post# of 157279
In this article, scientists explain that they have identified the LILRB4 hormone as a target for cancer therapy. If you search to see if a CCR5 antagonist can suppress this hormone you find that both are unique and do not act on one another. However, you can suppress LIL by suppressing myeloid-derived suppressor cells MDSCs. You can suppress MDSCs with an IL6 antagonist. Hmmm, I think Leronlimab will do all of this, by blocking CCR5. It all comes back to what we have. I think suppression of LILRB4 hormone should be described in our mechanism of action.
Our management needs to address the slowness of our CRC clinical and get our data submitted! Time is not our friend!
https://www.sciencedaily.com/releases/2025/09...091002.htm
CCR5 antagonists inhibit the recruitment and immunosuppressive functions of myeloid-derived suppressor cells (MDSCs), making them a promising strategy for cancer immunotherapy. Research has shown that blocking the CCR5-chemokine axis can reduce the accumulation and activity of MDSCs in tumors, thereby enhancing anti-cancer immune responses. The role of the CCR5 axis in MDSC activity Recruitment and trafficking: The C-C chemokine receptor type 5 (CCR5) is expressed on MDSCs. Its ligands, such as CCL3, CCL4, and CCL5, are produced by tumor cells and the tumor microenvironment. This interaction is a key driver for mobilizing and recruiting MDSCs from the bone marrow and blood into tumor sites.Enhanced immunosuppression: Studies in melanoma and other cancers have shown that CCR5+ MDSCs are more immunosuppressive than their CCR5- counterparts. In melanoma, CCR5+ MDSCs produce higher levels of arginase-1, which suppresses T-cell function. Inflammatory factors, particularly IL-6, can upregulate CCR5 expression on MDSCs and increase their immunosuppressive capacity via the STAT3 pathway.Correlation with tumor progression: The accumulation of CCR5+ MDSCs in tumors and peripheral blood has been linked to increased tumor progression in both mouse models and human patients. How CCR5 antagonists affect MDSCs Blocking the CCR5-ligand interaction disrupts the MDSC-mediated immune suppression at multiple stages. Reduced migration: By antagonizing CCR5, these drugs directly inhibit the migration and accumulation of MDSCs at the tumor site, which is a key step for creating an immunosuppressive microenvironment.Impaired function: CCR5 antagonists can diminish the immunosuppressive potential of MDSCs. For example, blocking CCR5 signaling can reduce the expression of immunosuppressive factors like TGF-\(\beta \) and IL-10 by MDSCs.Synergistic anti-tumor effects: When combined with other therapies, CCR5 antagonists can significantly enhance the anti-cancer immune response.Immune checkpoint inhibitors: Combining the CCR5 antagonist maraviroc with a PD-1 inhibitor (pembrolizumab) has shown promise in clinical trials for metastatic colorectal cancer.Inhibiting compensatory pathways: Single-agent inhibitors targeting MDSC recruitment pathways, such as CCR2, can be ineffective due to compensatory mechanisms. Combining CCR5 inhibitors with other agents, like CXCR2 inhibitors, may be a more successful strategy. CCR5 antagonists in clinical research Several CCR5 inhibitors originally developed for HIV treatment are being repurposed for oncology. Maraviroc: An oral small-molecule inhibitor, maraviroc has been tested in clinical trials for colorectal cancer with liver metastases, where it was shown to have beneficial effects.Leronlimab: A monoclonal antibody against CCR5, leronlimab has been used in HIV patients and is being investigated for oncology applications.Other agents: Other CCR5-targeting agents, such as the fusion protein mCCR5-Ig and the natural product anibamine, have shown promise in preclinical studies. Overall, targeting the CCR5 axis is a viable strategy to disrupt MDSC function, reduce tumor immunosuppression, and improve the efficacy of other immunotherapies.
In a potential cancer immunotherapy strategy, suppressing myeloid-derived suppressor cells (MDSCs) with an Interleukin-6 (IL-6) antagonist would indirectly inhibit the activity of the immune checkpoint receptor LILRB4 (leukocyte immunoglobulin-like receptor subfamily B member 4). High levels of IL-6 promote MDSC activity, and the LILRB4 receptor on these cells drives their immunosuppressive function. By blocking the IL-6 pathway, the expansion and function of MDSCs are curtailed, thereby reducing the overall immunosuppressive effects they exert, including those mediated by LILRB4.
Our management needs to address the slowness of our CRC clinical and get our data submitted! Time is not our friend!
https://www.sciencedaily.com/releases/2025/09...091002.htm
CCR5 antagonists inhibit the recruitment and immunosuppressive functions of myeloid-derived suppressor cells (MDSCs), making them a promising strategy for cancer immunotherapy. Research has shown that blocking the CCR5-chemokine axis can reduce the accumulation and activity of MDSCs in tumors, thereby enhancing anti-cancer immune responses. The role of the CCR5 axis in MDSC activity Recruitment and trafficking: The C-C chemokine receptor type 5 (CCR5) is expressed on MDSCs. Its ligands, such as CCL3, CCL4, and CCL5, are produced by tumor cells and the tumor microenvironment. This interaction is a key driver for mobilizing and recruiting MDSCs from the bone marrow and blood into tumor sites.Enhanced immunosuppression: Studies in melanoma and other cancers have shown that CCR5+ MDSCs are more immunosuppressive than their CCR5- counterparts. In melanoma, CCR5+ MDSCs produce higher levels of arginase-1, which suppresses T-cell function. Inflammatory factors, particularly IL-6, can upregulate CCR5 expression on MDSCs and increase their immunosuppressive capacity via the STAT3 pathway.Correlation with tumor progression: The accumulation of CCR5+ MDSCs in tumors and peripheral blood has been linked to increased tumor progression in both mouse models and human patients. How CCR5 antagonists affect MDSCs Blocking the CCR5-ligand interaction disrupts the MDSC-mediated immune suppression at multiple stages. Reduced migration: By antagonizing CCR5, these drugs directly inhibit the migration and accumulation of MDSCs at the tumor site, which is a key step for creating an immunosuppressive microenvironment.Impaired function: CCR5 antagonists can diminish the immunosuppressive potential of MDSCs. For example, blocking CCR5 signaling can reduce the expression of immunosuppressive factors like TGF-\(\beta \) and IL-10 by MDSCs.Synergistic anti-tumor effects: When combined with other therapies, CCR5 antagonists can significantly enhance the anti-cancer immune response.Immune checkpoint inhibitors: Combining the CCR5 antagonist maraviroc with a PD-1 inhibitor (pembrolizumab) has shown promise in clinical trials for metastatic colorectal cancer.Inhibiting compensatory pathways: Single-agent inhibitors targeting MDSC recruitment pathways, such as CCR2, can be ineffective due to compensatory mechanisms. Combining CCR5 inhibitors with other agents, like CXCR2 inhibitors, may be a more successful strategy. CCR5 antagonists in clinical research Several CCR5 inhibitors originally developed for HIV treatment are being repurposed for oncology. Maraviroc: An oral small-molecule inhibitor, maraviroc has been tested in clinical trials for colorectal cancer with liver metastases, where it was shown to have beneficial effects.Leronlimab: A monoclonal antibody against CCR5, leronlimab has been used in HIV patients and is being investigated for oncology applications.Other agents: Other CCR5-targeting agents, such as the fusion protein mCCR5-Ig and the natural product anibamine, have shown promise in preclinical studies. Overall, targeting the CCR5 axis is a viable strategy to disrupt MDSC function, reduce tumor immunosuppression, and improve the efficacy of other immunotherapies.
In a potential cancer immunotherapy strategy, suppressing myeloid-derived suppressor cells (MDSCs) with an Interleukin-6 (IL-6) antagonist would indirectly inhibit the activity of the immune checkpoint receptor LILRB4 (leukocyte immunoglobulin-like receptor subfamily B member 4). High levels of IL-6 promote MDSC activity, and the LILRB4 receptor on these cells drives their immunosuppressive function. By blocking the IL-6 pathway, the expansion and function of MDSCs are curtailed, thereby reducing the overall immunosuppressive effects they exert, including those mediated by LILRB4.
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