免疫学系Jason B. Muhitch研究小组的研究显示，综合肿瘤免疫谱揭示了类肉瘤肾细胞癌中矛盾免疫敏感性的介质。相关论文发表在2025年8月7日出版的《癌细胞》杂志上。

为了更好地理解这种矛盾的免疫敏感性的微环境介质，研究组对人类sRCC肿瘤进行了单细胞分析，并将其与透明细胞RCC （ccRCC）进行了比较，并在空间和大量转录组数据集中验证了3000多个RCC肿瘤。课题组研究人员在这些正交方法中描述了sRCC中的一个机器人免疫网络：sRCC中的肿瘤浸润T细胞更活跃，随后被耗尽，同时被CXCL13表达富集。与此同时，三级淋巴结构在sRCC中普遍存在，与体液免疫活性的功能富集平行。肿瘤克隆分析显示，sRCC中铁相关程序增加，呈现出潜在的脆弱性。该课题组进一步利用sRCC的矛盾生物学来获得基因组去分化特征（GDS），该特征虽然预后不良，但可以识别出最可能从ICB中受益的患者，包括队列和肿瘤类型。

据悉，具有肉瘤样特征的肾细胞癌（sRCC）是一种高度侵袭性的肿瘤类型，但免疫检查点阻断（ICB）优先响应。

附：英文原文

Title: Comprehensive tumor-immune profiling reveals mediators of paradoxical immune sensitivity in sarcomatoid renal cell carcinoma

Author: Nicholas J. Salgia, Adil Khan, Wilhelm M. Aubrecht, Gavin C. Twoey, Jacky Chow, Kristopher Attwood, Han Yu, Jessie L. Chiello, Nathaniel Hansen, Brianna J. Wasik, Benjamin D. Mercier, Hedyeh Ebrahimi, Luis Meza, Orla Maguire, Michalis Mastri, Cassandra Whalen, Hans Minderman, Patrick Pirrotte, Sara Byron, Elizabeth A. Repasky, Prashant K. Singh, Wiam Bshara, Jianmin Wang, A.J. Robert McGray, Scott I. Abrams, Bo Xu, Kevin H. Eng, Mark D. Long, Sumanta K. Pal, Eric C. Kauffman, Jason B. Muhitch

Issue&Volume: 2025-08-07

Abstract: Renal cell carcinoma with sarcomatoid features (sRCC) is a highly aggressive tumor type yet preferentially responds to immune checkpoint blockade (ICB). To better understand microenvironmental mediators of this paradoxical immune sensitivity, we performed single-cell analyses of human sRCC tumors compared against clear cell RCC (ccRCC), with validation spatially and in bulk transcriptomic datasets totaling over 3,000 RCC tumors. We describe a robust immune network in sRCC using these orthogonal approaches: tumor-infiltrating T cells in sRCC are more activated, and subsequently exhausted, while being enriched for CXCL13 expression. Congruently, tertiary lymphoid structures are pervasive in sRCC, paralleling functional enrichment of humoral immune activity. Tumor clone analysis revealed increased iron-associated programs in sRCC, presenting a potential vulnerability. We furthermore leveraged the paradoxical biology of sRCC to derive a genomic dedifferentiation signature (GDS) that, while negatively prognostic, identifies patients most likely to benefit from ICB across cohorts and tumor types.

DOI: 10.1016/j.ccell.2025.07.010

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00316-2