CD163⁺肿瘤相关巨噬细胞与转移性透明细胞肾细胞癌患者一线纳武利尤单抗治疗的临床结果：来自HCRN GU16-260试验的启示.pdf

1、CD163 Tumor-Associated Macrophages and Clinical Outcomes to First-Line Nivolumab Therapy in Patients with Metastatic Clear Cel Renal Cell Carcinoma:Insights from the HCRN GU16-260 Trial Berkay Simsek,MDBrigham&Womens Hospital,Harvard Medical School7/18/2025Disclosures No disclosuresTAMs inhibit anti

2、-tumor immunity and modulate response to immune checkpoint inhibitors(ICI)TAMs promote immunosuppression Although TAMs have been associated with resistance to ICI in several cancer types(CRC,PDAC),the association with response has been also reported(HL)The role of TAMs as predictors of clinical outc

3、omes to ICI in clear cell RCC remains unclearRuffell,B.&Coussens,Cancer Cell 2015;Wener et al,Sci Rep 2020 TAMs promote T cell exhaustion in preclinical modelsAdapted from Kersten et al,Cancer Cell 2022 Chemokines secreted from T lymphocytes recruit monocytes into TME Monocytes develop into TAMs Ine

4、ffective TCR interactions between TAMs and lymphocytes Secretion of immunosuppressive cytokines into TMEAims1)To assess the association of CD163 TAMs with clinical outcomes to first-line nivolumab therapy in metastatic clear cell renal cell carcinoma(mccRCC)2)To investigate whether TAMs and exhauste

5、d CD8+TILs reside and interact within a spatially defined nichePhenotype DefinitionsTAMCD163+Non-terminally exhausted CD8 TILCD8+PD1+TIM3-LAG3-Terminally exhausted CD8 TILCD8+PD1+TIM3+and/orLAG3+Methods-1Pre-treatment tumor samples from 67 patients enrolled in the HCRN clinical trial of first-line n

6、ivolumab therapy in mccRCCDensities of immune cell populations were calculatedStatistical/bioinformatics analysesAim 1:Associations of density of CD163 TAMs with progression-free survival(PFS)and objective response rate(ORR)were assessed using univariable Cox and logistic regression models,respectiv