CELL INTELLIGENCE · 肿瘤细胞治疗研究

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PD-1(+)Tim-3(+)CD103(+) CD8(+) TIL（肿瘤浸润淋巴细胞）与结直肠癌良好结局相关

英文原题：PD-1(+)Tim-3(+)CD103(+) CD8(+) Tumor-infiltrating Lymphocytes Are Associated With Favorable Outcomes in Colorectal Cancer.

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PD-1(+)Tim-3(+)CD103(+) CD8(+) Tumor-infiltrating Lymphocytes Are Associated With Favorable Outcomes in Colorectal Cancer.

PubMed 2026/05/01（内容时间） Anticancer Res Q4 · IF 1.8（JCR 2025）

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结直肠癌地区：日本
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研究概要

CRC 中 PD-1 + Tim-3 + CD103 + CD8 + T 细胞的高频率与更好的生存相关，突显了其作为预后生物标志物和治疗靶点的潜力。

研究思路结论见上方概要

背景

结直肠癌（CRC）仍然是全球癌症相关死亡的主要原因，迫切需要开发新的治疗策略。肿瘤免疫微环境（TME）对疾病进展和免疫检查点抑制剂（ICIs）的应答具有关键影响。TIL（肿瘤浸润淋巴细胞）（TILs）是TME的关键组成部分，具有已确立的预后和预测意义。然而，使用流式细胞术对CRC中TIL进行详细表征尚未得到充分研究。

方法

我们采用多色流式细胞术分析了90份新鲜CRC标本中的TIL，以研究特定T细胞亚群与临床结局之间的关联。根据TIL标志物表达的分层聚类，将患者分为Hot组和Cold组。

结果

Hot 组的总生存期（OS）显著优于 Cold 组（5 年 OS：86.7% vs. 63.9%，p=0.006），尽管无复发生存期（RFS）无显著差异（5 年 RFS：79.5% vs. 66.1%，p=0.24）。CITRUS 分析显示，PD-1 + Tim-3 + CD103 + CD8 + T 细胞在热肿瘤中富集（32.1% vs. 6.1%，p<0.001），并与良好预后相关。重要的是，多因素分析表明，CD8 + T 细胞中 PD-1 + Tim-3 + CD103 + 细胞频率低是 OS 的独立预后因素[风险比（HR）=3.36，95% 置信区间（CI）=1.20-9.34，p=0.02]。

展开英文摘要原文
MATERIALS AND METHODS

We analyzed TILs from 90 fresh CRC specimens using multicolor flow cytometry to investigate the association between specific T cell subsets and clinical outcomes. Patients were classified into Hot and Cold groups based on hierarchical clustering of TIL marker expression.

RESULTS

The Hot group demonstrated significantly better overall survival (OS) compared to the Cold group (5-year OS: 86.7% vs . 63.9%, p =0.006), although recurrence-free survival (RFS) was not significantly different (5-year RFS: 79.5% vs . 66.1%, p =0.24). CITRUS analysis revealed that PD-1 + Tim-3 + CD103 + CD8 + T cells were enriched in hot tumors (32.1% vs . 6.1%, p <0.001) and correlated with a favorable prognosis. Importantly, multivariate analysis demonstrated that a low frequency of PD-1 + Tim-3 + CD103 + cells among CD8 + T cells was an independent prognostic factor for OS [hazard ratio (HR)=3.36, 95% confidence interval (CI)=1.20-9.34, p =0.02].

CONCLUSION

A high frequency of PD-1 + Tim-3 + CD103 + CD8 + T cells is associated with better survival in CRC, highlighting their potential as a prognostic biomarker and therapeutic target.

论文信息

作者
Matoba D、Saito T、Noda T、Uemura M、Ueyama A、Wada H、Doki Y、Eguchi H
第一作者单位
Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Osaka, Japan.Japan
通讯作者单位
Department of Gastroenterological Surgery, Graduate School of Medicine, The University of Osaka, Osaka, Japan; tsaito@gesurg.med.osaka-u.ac.jp.Japan
期刊
Anticancer research2026 May
原文标识
PubMed 42049323　·　DOI 10.21873/anticanres.18125

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