CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival.
Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival.
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用免疫检查点抑制剂或共刺激因子重新激活肿瘤浸润T淋巴细胞（TILs）已被证明是一种对多种恶性肿瘤有效的抗癌策略。然而，上皮性卵巢癌（EOC）在很大程度上仍对当前靶向T细胞的免疫治疗无效。因此，有必要识别具有EOC预后价值的新型免疫检查点靶点和生物标志物。结合多色免疫荧光染色与单细胞RNA测序分析，我们在此鉴定了EOC中一个TIM-3/CXCL13阳性的组织驻留记忆（CD8/CD103阳性）T细胞（Trm）群体。对约175例高级别浆液性EOC患者队列的分析显示，TIM-3阳性Trm与患者生存改善显著相关。由于CXCL13阳性CD8阳性T细胞与患者对抗PD1免疫检查点阻断的应答密切相关，联合TIM-3和PD-1阻断治疗可能对EOC中抗癌免疫的（再）激活具有重要意义。
Reactivation of tumor infiltrating T lymphocytes (TILs) with immune checkpoint inhibitors or co-stimulators has proven to be an effective anti-cancer strategy for a broad range of malignancies.
However, epithelial ovarian cancer (EOC) remains largely refractory to current T cell-targeting immunotherapeutics.
Therefore, identification of novel immune checkpoint targets and biomarkers with prognostic value for EOC is warranted. Combining multicolor immunofluorescent staining's with single cell RNA-sequencing analysis, we here identified a TIM-3/CXCL13-positive tissue-resident memory (CD8/CD103-positive) T cell (Trm) population in EOC.
Analysis of a cohort of ~175 patients with high-grade serous EOC revealed TIM-3-positive Trm were significantly associated with improved patient survival. As CXCL13-positive CD8-positive T cells have been strongly linked to patient response to anti-PD1 immune checkpoint blockade, combinatorial TIM-3 and PD-1 blockade therapy may be of interest for the (re)activation of anti-cancer immunity in EOC.
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