免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
黑色素瘤中 CD103⁺CD8⁺ 组织驻留记忆 T 淋巴细胞增强抗肿瘤免疫并预测免疫治疗结局
英文原题：CD103(+)CD8(+) tissue-resident memory T lymphocytes of melanoma boost anti-tumour immunity and predict immunotherapy outcomes.
查看英文原题
CD103(+)CD8(+) tissue-resident memory T lymphocytes of melanoma boost anti-tumour immunity and predict immunotherapy outcomes.
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研究概要
黑色素瘤中的 CD103 + CD8 + TRM 细胞在抗肿瘤免疫过程中发挥关键作用，也可作为免疫治疗疗效的可靠预测指标。
中文摘要
背景
免疫治疗通过重新激活抗肿瘤免疫系统，显著改善了黑色素瘤治疗。CD8+组织驻留记忆T淋巴细胞（CD8+ TRM）已成为抗肿瘤免疫的重要介质，但其在黑色素瘤中的特定作用仍不清楚。
方法
将CD8+ CD45.1+ OT-1细胞过继转移至CD45.2+小鼠后，采用磁分选纯化并分析驻留记忆CD8+ T细胞（TRM）。通过多重免疫组化评估ZS黑色素瘤队列中CD8+ TRM的空间分布；结合单细胞RNA测序、空间转录组及体内外实验，研究CD8+ TRM的生物学功能及其对抗肿瘤免疫的影响。最后，在多个独立队列中评估CD8+ TRM作为免疫治疗应答预测指标的价值。
结果
CD8+ TRM在黑色素瘤中具有强效肿瘤杀伤能力，CD103是其特征性标志。肿瘤组织中CD103+ CD8+ TRM浸润较高与黑色素瘤患者预后改善显著相关。体内过继转移CD103+ CD8+ TRM可有效抑制黑色素瘤进展。机制上，CD103可激活整合素依赖的PI3K/AKT信号级联，促进CD8+ TRM增殖并增强其抗肿瘤效应功能。值得注意的是，CD103+ CD8+ TRM优先定位于三级淋巴结构（TLS）内，过继转移该细胞还可促进TLS形成。临床上，CD103+ CD8+ TRM在免疫治疗应答者中富集，可有力预测免疫检查点阻断（ICB）治疗结局。
结论
黑色素瘤中的CD103+ CD8+ TRM在抗肿瘤免疫过程中发挥关键作用，也可作为可靠的免疫治疗疗效预测指标。要点：CD103是黑色素瘤组织驻留记忆CD8+ T细胞的可靠标志；CD103+ CD8+ TRM具有强效抗肿瘤免疫活性；该细胞可预测黑色素瘤患者对免疫治疗的良好应答。
展开英文摘要原文
BACKGROUND
Immunotherapy has revolutionised melanoma treatment, providing significant clinical benefits by reactivating the anti-tumour immune system. CD8 + tissue-resident memory T lymphocytes (CD8 + TRM) have emerged as crucial mediators of anti-tumour immunity, while their specific role in melanoma remains poorly understood.
METHODS
Following CD8 + CD45.1 + OT-1 cell adoptive transfer into CD45.2 + mice, we employed magnetic separation to purify and analyse resident memory CD8 + T cells (TRM). We use multiple immunohistochemistry (mIHC) to evaluate the spatial distribution of CD8 + TRM in ZS melanoma cohort. Additionally, the biological function of CD8 + TRM and their impact on anti-tumour immunity are explored using scRNA sequencing and spatial transcriptomics, coupled with in vivo/in vitro experiments. Finally, CD8 + TRM utility as an immunotherapy response predictor is examined across several independent cohorts.
RESULTS
CD8 + TRM demonstrates potent tumour-killing capabilities in melanoma, with CD103 as a distinctive marker. High CD103 + CD8 + TRM infiltration in tumour tissues strongly correlates with improved prognosis in melanoma patients. In vivo adoptive transfer of CD103 + CD8 + TRM effectively inhibits melanoma progression. Mechanistically, CD103 activates the integrin-dependent PI3K/AKT signalling cascade, promoting both proliferation and anti-tumour effector functions of CD8 + TRM. Notably, CD103 + CD8 + TRM preferentially localises within tertiary lymphoid structures (TLS), and its adoptive transfer promotes TLS formation. Clinically, CD103 + CD8 + TRM is enriched in immunotherapy-responsive patients and serves as a strong predictor for immune checkpoint blockade (ICB) treatment outcomes.
CONCLUSIONS
CD103 + CD8 + TRM cells in melanoma play a key role in the anti-tumour immune process and can also be used as a reliable predictor of immunotherapy efficacy. KEY POINTS: CD103 is a reliable marker of tissue-resident memory (TRM) CD8 + T cells in melanoma. CD103 + CD8 + TRM cells exhibit potent anti-tumour immune activity. CD103 + CD8 + TRM cells predict favourable responses to immunotherapy in melanoma.
论文信息
- 作者
- Zhang T、Song J、Li Y、Shen K、Xuan J、Gao Y、Lu L、Pang Z
- 单位
- Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, PR China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Clinical and translational medicine2025 Sep
- 原文标识
- PubMed 40985995 · DOI 10.1002/ctm2.70464
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