Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Br J Cancer. 2022 Jun;126(11):1581-1588. doi: 10.1038/s41416-022-01725-6. Epub 2022 Feb 14.
CD103CD8 tissue-resident memory T (T) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT).
Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103CD8 T cells.
Patients with high CD103CD8 T cells infiltration, but not CD8 T cells, are more likely to benefit from immunotherapy and ACT. The presence of T cells is highly associated with an enhanced IFNγ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103CD8 T cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients.
CD103CD8 T cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients.
CD103CD8 组织驻留记忆 T(T)细胞与多种恶性肿瘤的总体生存率提高有关,被认为能激活抗肿瘤免疫反应,并影响治疗敏感性,包括免疫治疗和辅助化疗(ACT)。
本研究共纳入了来自三个独立队列的 650 例肌层浸润性膀胱癌(MIBC)患者进行生存和基于顺铂的 ACT 反应分析。另一项由接受 PD-L1 阻断的 195 例 IMvigor210 试验患者组成的公共数据集用于评估免疫治疗反应。59 份新鲜肿瘤组织用于评估 CD103CD8 T 细胞的免疫浸润。
高 CD103CD8 T 细胞浸润而非 CD8 T 细胞浸润的患者更可能从免疫治疗和 ACT 中获益。T 细胞的存在与增强的 IFNγ 富集和 T 细胞浸润性抗肿瘤微环境高度相关。CD103CD8 T 细胞浸润的增加与错配修复(MMR)、同源重组(HR)、PI3KCA/AKT 和 RAS/RAF 通路功能正常或组蛋白修饰和细胞周期通路缺陷患者的 ACT 反应较好相关。
CD103CD8 T 细胞在抗肿瘤免疫中发挥关键作用,是一个理想的预后生物标志物。它可以作为 MIBC 患者对 PD-L1 抑制剂和 ACT 治疗反应的一个优越的伴随预测因子。