Prevalence of tumour-infiltrating CD103+ cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome
Prevalence of tumour-infiltrating CD103+ cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome
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肿瘤浸润 CD103 细胞的普遍存在可识别临床结果较差的治疗敏感前列腺癌
DOI：
10.1038/s41416-023-02183-4
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发表时间：
2023-02-09
影响因子：
8.8
通讯作者：
Jiang, Haowen
中科院分区：
文献类型：
--
作者：
Zhou, Quan;Ou, Yuxi;Jiang, Haowen
背景技术背景：前列腺癌（PCa）中CD 103（+）细胞的临床意义和免疫相关性仍在探索中。方法：共纳入3个队列的1080例接受根治性前列腺癌切除术的患者进行回顾性分析。肿瘤微阵列的构建和新鲜的肿瘤样本进行了流式细胞仪分析。结果：高CD 103（+）细胞浸润与减少生化复发（BCR）的生存PCa。辅助激素治疗（HT）延长了CD 103（+）细胞丰度高风险淋巴结阴性疾病的无BCR生存期。PCa中CD 103（+）细胞浸润与细胞毒性表达减少以及CD 8（+）和CD 4（+）T细胞、M1巨噬细胞和肥大细胞浸润增加相关。肿瘤内CD 8（+）T细胞是CD 103的主要来源，CD 103 + CD 8（+）T细胞亚群以高表达IL-10、PD-1和CTLA-4为特征。肿瘤浸润CD 103（+）CD 8（+）T细胞发挥抗肿瘤功能时，HT exvivo.DISCUSSION治疗：CD 103（+）细胞浸润预测无BCR生存和对辅助HT PCa。CD 103（+）细胞浸润与丰富但免疫逃避的免疫景观相关。该研究支持了一种模型，即CD 103表达对肿瘤浸润的CD 8（+）T细胞具有负面预后影响和免疫抑制功能，而CD 103（+）CD 8（+）T细胞对HT具有强大的抗肿瘤免疫力。
BACKGROUND: The clinical significance and immune correlation of CD103(+) cells in prostate cancer (PCa) remain explored.METHODS: In total, 1080 patients with PCa underwent radical prostatectomy from three cohorts were enrolled for retrospective analysis. Tumour microarrays were constructed and fresh tumour samples were analysed by flow cytometry.RESULTS: High CD103(+) cell infiltration correlated with reduced biochemical recurrence (BCR)-free survival in PCa. Adjuvant hormone therapy (HT) prolonged the BCR-free survival for high-risk node-negative diseases with CD103(+) cell abundance. CD103(+) cell infiltration correlated with less cytotoxic expression and increased infiltration of CD8(+) and CD4(+) T cells, M1 macrophages and mast cells in PCa. Intratumoral CD8(+) T cell was the predominant source of CD103, and the CD103+ subset of CD8(+) T cells was featured with high IL-10, PD-1 and CTLA-4 expression. Tumour-infiltrating CD103(+) CD8(+) T cells exerted anti-tumour function when treated with HT ex vivo.DISCUSSION: CD103(+) cell infiltration predicted BCR-free survival and response to adjuvant HT in PCa. CD103(+) cell infiltration correlated with an enriched but immune-evasive immune landscape. The study supported a model that CD103 expression conferred negative prognostic impact and immunosuppressive function to tumour-infiltrating CD8(+) T cells, while the CD103(+) CD8(+) T cells exhibited a powerful anti-tumour immunity with response to HT.