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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Cell Line, Tumor, Chemokine CCL3, Chemokine CXCL5, Gene Expression Regulation, Neoplastic, Humans, Interleukin-1beta, Interleukin-8, Mice, Monocytes, Myeloid-Derived Suppressor Cells, Parenchymal Tissue, Programmed Cell Death 1 Receptor, Receptors, Interleukin-8B, Tumor Burden.
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Is myeloid derived suppressor cell subset accumulation in renal cell carcinoma parenchyma associated with intratumoral expression of IL-1β , IL-8 , CXCL5 and Mip-1α? Context: Little is known about the association between MDSC subsets and various chemokines in patients with RCC, or the factors that draw MDSC into tumor parenchyma. We analyzed PMN-MDSC, M-MDSC and I-MDSC from the parenchyma and peripheral blood of 48 RCC patients, isolated at nephrectomy. We analyzed levels of IL-1β, IL-8, CXCL5, Mip-1α, MCP-1 and Rantes. Furthermore, we performed experiments in a Renca murine model to assess therapeutic synergy between CXCL2 and anti-PD1, and to elucidate the impact of IL-1β blockade on MDSC. Parenchymal PMN-MDSC have a positive correlation with IL-1β, IL-8, CXCL-5 and Mip-1α, and I-MDSC correlate with IL-8 and CXCL-5. Furthermore, peripheral PMN-MDSC correlate with tumor grade. Given that PMN-MDSC express CXCR2, and parenchymal PMN-MDSC correlated with IL-8 and CXCL5, we assessed the response of CXCR2 blockade with or without anti-PD1. Combination therapy reduced tumor weight and enhanced CD4+ and CD8+ T cell infiltration. In addition, anti-IL1β decreased PMN and M-MDSC in the periphery, PMN-MDSC in the tumor, and peripheral CXCL5 and KC. Anti-IL1β also delayed tumor growth.
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Parenchymal PMN-MDSC have a positive correlation with IL-1 β, IL-8, CXCL-5 and Mip-1α, suggesting they may attract PMN-MDSC into the tumor. Peripheral PMN-MDSC correlate with tumor grade, suggesting prognostic significance. Anti-CXCR2 and anti-PD1 synergized to reduce tumor weight and enhanced CD4+ and CD8+ T cell infiltration in a Renca model, suggesting that CXCR2+ PMN-MDSC are important in reducing activity of anti-PD-1 antibody.Lastly, anti-IL1β decreases MDSC and delayed tumor growth, suggesting a potential target for MDSC inhibition. Final Decision: yes