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CD103CD8 组织驻留记忆 T 细胞浸润预测肌肉浸润性膀胱癌的临床结局和辅助治疗获益。

CD103CD8 tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer.

机构信息

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.

出版信息

Br J Cancer. 2022 Jun;126(11):1581-1588. doi: 10.1038/s41416-022-01725-6. Epub 2022 Feb 14.

Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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)。

方法

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。

结果

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。

结论

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。

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