Ishihara Hiroki, Fukuda Hironori, Mizoguchi Yukihiro, Yamashita Makiko, Aoki Kazunori, Ishiyama Ryo, Ikeda Takashi, Nemoto Yuki, Shimmura Hiroaki, Hashimoto Yasunobu, Yoshida Kazuhiko, Hirai Toshihito, Iizuka Junpei, Tokita Daisuke, Kondo Tsunenori, Nagashima Yoji, Takagi Toshio
Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, Japan.
Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, Japan.
Cancer Immunol Immunother. 2025 Jan 3;74(2):51. doi: 10.1007/s00262-024-03876-2.
Sex differences in the outcomes of advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) and the profiles of tumor-infiltrating immune cells (TIICs) remain unclear. We retrospectively evaluated data from 563 patients with RCC receiving systemic therapy, including first-line dual ICI combinations (i.e., immunotherapy [IO]-IO), combinations of ICIs with tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI), TKI monotherapy, and subsequent nivolumab monotherapy. Survival and tumor response were compared between the sexes in each treatment group, and TIIC profiles were compared using 116 RCC tumor samples analyzed by flow cytometry. Progression-free survival (PFS) was shorter in female than in male patients in the IO-IO (p = 0.0227) and nivolumab monotherapy (p = 0.0478) groups. Furthermore, sex remained an independent factor for shorter PFS after adjusting for covariates in the IO-IO (p = 0.0340) and nivolumab monotherapy (p = 0.0322) groups. In contrast, PFS was not significantly different between sexes in the IO-TKI or TKI monotherapy groups (p > 0.05). Overall survival and objective response rates were not significantly different between the sexes in any of the treatment groups (p > 0.05). Some TIIC populations, including that of CD8 + T cells (p = 0.0096), decreased to a greater extent in female than in male patients in the advanced-stage population. In conclusion, the effectiveness of ICIs on PFS was lower in female patients than in male patients, potentially because of the different profiles of the immune microenvironment, particularly the decreased number of CD8 + T cells in females.
免疫检查点抑制剂（ICI）治疗晚期肾细胞癌（RCC）的疗效性别差异以及肿瘤浸润免疫细胞（TIIC）的特征仍不明确。我们回顾性评估了563例接受全身治疗的RCC患者的数据，包括一线双联ICI组合（即免疫疗法[IO]-IO）、ICI与酪氨酸激酶抑制剂（TKI）的组合（即IO-TKI）、TKI单药治疗以及后续的纳武单抗单药治疗。比较了各治疗组中不同性别的生存和肿瘤反应，并使用通过流式细胞术分析的116份RCC肿瘤样本比较了TIIC特征。在IO-IO组（p = 0.0227）和纳武单抗单药治疗组（p = 0.0478）中，女性患者的无进展生存期（PFS）短于男性患者。此外，在IO-IO组（p = 0.0340）和纳武单抗单药治疗组（p = 0.0322）中，调整协变量后，性别仍是PFS较短的独立因素。相比之下，IO-TKI组或TKI单药治疗组中不同性别之间的PFS无显著差异（p>0.05）。在任何治疗组中，不同性别之间的总生存期和客观缓解率均无显著差异（p>0.05）。在晚期人群中，包括CD8 + T细胞群体（p = 0.0096）在内的一些TIIC群体在女性患者中的减少程度大于男性患者。总之，ICI对女性患者PFS的疗效低于男性患者，这可能是由于免疫微环境的不同特征，特别是女性CD8 + T细胞数量减少所致。
