借力推动前列腺癌 CAR-T 细胞治疗进展
Piggybacking toward Progress for CAR T-Cell Therapy in Prostate Cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤浸润性 CD103(+) 细胞的流行率可识别治疗敏感但临床预后不良的前列腺癌
英文原题：Prevalence of tumour-infiltrating CD103(+) cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome.
查看英文原题
Prevalence of tumour-infiltrating CD103(+) cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome.
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研究概要
CD103+细胞浸润预测了 PCa 中无 BCR 生存期和对辅助 HT 的应答。CD103+细胞浸润与富集但免疫逃逸的免疫景观相关。该研究支持一个模型，即 CD103 表达赋予肿瘤浸润 CD8+T 细胞不良预后影响和免疫抑制功能，而 CD103+CD8+T 细胞则表现出强大的抗肿瘤免疫并对 HT 有应答。
研究思路结论见上方概要
背景
CD103+细胞在前列腺癌（PCa）中的临床意义及免疫相关性仍有待探索。
方法
共有来自三个队列的1080例PCa患者接受了根治性前列腺切除术，纳入回顾性分析。构建了肿瘤组织芯片，并通过流式细胞术分析了新鲜肿瘤样本。
结果
高 CD103 + 细胞浸润与 PCa 中生化复发（BCR）无生存期缩短相关。辅助激素治疗（HT）延长了 CD103 + 细胞丰富的高危淋巴结阴性疾病的 BCR 无生存期。CD103 + 细胞浸润与 PCa 中细胞毒性表达减少以及 CD8 + 和 CD4 + T 细胞、M1 巨噬细胞和肥大细胞浸润增加相关。瘤内 CD8 + T 细胞是 CD103 的主要来源，CD8 + T 细胞的 CD103 + 亚群以高 IL-10、PD-1 和 CTLA-4 表达为特征。肿瘤浸润 CD103 + CD8 + T 细胞在体外接受 HT 治疗时发挥抗肿瘤功能。
展开英文摘要原文
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.
论文信息
- 作者
- Zhou Q、Ou Y、Dai X、Chen X、Wu S、Chen W、Hu M、Yang C
- 第一作者单位
- Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.China
- 通讯作者单位
- Department of Urology, Huashan Hospital, Fudan University, Shanghai, China. haowj_sh@fudan.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- British journal of cancer2023 Apr
- 原文标识
- PubMed 36759726 · DOI 10.1038/s41416-023-02183-4
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