There is a need to optimize the treatment of clear cell renal cell carcinoma (ccRCC) patients at high recurrence risk after nephrectomy. We sought to elucidate the tumor immune microenvironment (TIME) of localized ccRCC and understand the prognostic and predictive characteristics of certain features. The discovery cohort was clinically localized patients in the TCGA-Kidney Renal Clear Cell Carcinoma (KIRC) project (n= 382). We identified an M0 macrophage-enriched cluster (n= 25) in the TCGA-KIRC cohort. This cluster’s median progression-free survival (PFS) and overall survival (OS) were 40.4 and 45.3 months, respectively, but this was not reached in the others (p= 0.0003 and <0.0001, respectively). Gene set enrichment (GSEA) analysis revealed an enrichment of epithelial to mesenchymal transition and cell cycle progression genes within this cluster, and these patients also had a lower predicted response to immune checkpoint blockade (ICB) (4% vs. 20–34%). An M0-enriched cluster (n= 9) with shorter PFS (p= 0.0006) was also identified in the Clinical Proteomics Tumor Analysis Consortium (CPTAC) cohort (n= 94). Through this characterization of the TIME in ccRCC, a cluster of patients defined by enrichment in M0 macrophages was identified that demonstrated poor prognosis and lower predicted ICB response. Pending further validation, this signature can identify localized ccRCC patients at high risk of recurrence after nephrectomy and who may require therapeutic approaches beyond ICB monotherapy.
对于肾切除术后高复发风险的透明细胞肾细胞癌（ccRCC）患者，其治疗方案有待优化。本研究旨在阐明局限性ccRCC的肿瘤免疫微环境（TIME），并探究特定特征的预后及预测价值。我们在TCGA肾透明细胞癌（KIRC）项目中选取了382例临床局限性患者作为发现队列，从中识别出一个富含M0巨噬细胞的亚群（n=25）。该亚群的中位无进展生存期（PFS）和总生存期（OS）分别为40.4个月和45.3个月，而其他患者均未达到该终点（p值分别为0.0003和<0.0001）。基因集富集分析显示该亚群中上皮-间质转化和细胞周期进程相关基因显著富集，且这些患者对免疫检查点阻断（ICB）的预测应答率较低（4% vs. 20-34%）。在临床蛋白质组肿瘤分析联盟（CPTAC）队列（n=94）中，同样发现了一个富含M0巨噬细胞且PFS较短（p=0.0006）的亚群（n=9）。通过对ccRCC肿瘤免疫微环境的特征分析，我们鉴定出一个以M0巨噬细胞富集为特征的ccRCC患者亚群，该亚群预后较差且对ICB的预测应答率较低。该特征谱经进一步验证后，可用于识别肾切除术后高复发风险、且可能需要超越ICB单药治疗的局限性ccRCC患者。
肿瘤(癌症)患者之家