← 返回

按部位划分的 B 与 T TIL(肿瘤浸润淋巴细胞)亚型:结肠癌免疫表型图谱

英文原题:B and T Tumor-Infiltrating Lymphocyte Subtypes According to Subsite: A Colon Cancer Immunophenotyping Map.

查看英文原题

B and T Tumor-Infiltrating Lymphocyte Subtypes According to Subsite: A Colon Cancer Immunophenotyping Map.

PubMed 2025/11/23(内容时间) Biomedicines Q2 · IF 4.5(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

近期文献不断显示,结直肠癌中TIL(肿瘤浸润淋巴细胞)亚型与预后相关。尽管近端和远端结肠存在遗传、表观遗传及分子差异,TIL亚群的预后作用是否因肿瘤部位而异仍不清楚。本研究旨在按原发肿瘤部位,考察CD3⁺淋巴细胞(反映总体T细胞浸润)、CD8⁺细胞(标记细胞毒性效应T细胞)和CD73⁺细胞(免疫抑制调节因子)的价值。

采用全切片组织取样、热诱导表位修复、特异性一抗及DAB显色,测定结肠癌患者CD73⁺、CD3⁺和CD8⁺肿瘤浸润B、T细胞密度。使用QuPath细胞计数功能量化有核细胞和免疫阳性细胞比例,使用ImageJ通过颜色拆分和光密度评估染色强度。免疫分析综合强度与阳性率形成免疫反应评分,并通过受试者工作特征(ROC)曲线确定CD3⁺、CD8⁺和CD73⁺淋巴细胞的最佳截点。统计分析评估TIL表达与病理特征之间的潜在关联,并按原发肿瘤部位分层;采用Kaplan–Meier法进行生存分析。

共纳入100例患者。CD3⁺ T细胞表达最丰富,且右侧结肠更常见。CD3⁺总数在左侧肿瘤中与T分期及神经周围侵犯相关,在右侧结肠中与肿瘤分级相关。按肿瘤部位设定CD3⁺阈值后的相关分析显示,N分期较高与CD3⁺细胞值较低显著相关(p=0.0306);左侧结肠中,神经周围侵犯较多与CD3⁺ TIL值较低相关(p=0.0123)。此外,左侧结肠中CD8⁺值较低与较高T分期相关(p=0.0382)。生存分析未发现所比较组间有统计学显著差异。

结肠癌患者的TIL亚型随原发肿瘤部位而显著变化,并与不同临床病理特征相关。本探索性研究仍需更大样本验证,之后才能据TIL密度指导治疗。

展开英文摘要原文

Background: Accumulating evidence regarding the association between tumor-infiltrating lymphocyte (TIL) subtypes and prognosis in colorectal cancer has emerged recently in the literature. Whether the prognostic impact of TIL subsets is different according to tumor location remains unknown, despite genetic, epigenetic and molecular differences between the proximal and distal colon.

Our study aimed to investigate the value of CD3 + lymphocytes, reflecting overall T-cell infiltration, CD8 + cells identifying cytotoxic effector T-cells and CD73 + cells acting as a modulator of immunosuppression, stratified by primary tumor location. Methods: The density of CD73 + , CD3 + and CD8 + tumor-infiltrating B- and T-cells was determined in colon cancer patients using whole-section tissue sampling, heat-induced epitope retrieval, primary antibodies and DAB visualization. QuPath Cell counter function quantified nucleated cells and immune-positive percentages; ImageJ assessed staining intensity via color deconvolution and optical density. An Immunoreactive Score combined intensity and positivity for immune profiling. The Receiver Operating Characteristic (ROC) curve analysis was used to determine the optimal cut-off values for CD3 + , CD8 + and CD73 + lymphocytes.

Statistical analysis was performed in order to identify potential associations between TILs expression and pathological characteristics, according to the location of the primary tumor. Survival analysis was carried out using the Kaplan-Meier method. Results: A total of 100 patients were included in the study. CD3 + T-cells were the most abundantly expressed and were more predominantly encountered in the right colon.

Total CD3 + numbers were correlated with T stage and the presence of perineural invasion in left-sided tumors, as well as with tumor grading in the right colon. Correlation analysis based on CD3 + threshold values according to tumor location demonstrated a statistically significant association between a higher N stage and low CD3 + cell values ( p value = 0. 0306), and higher perineural invasion and low CD3 + TILs values in the left colon ( p value = 0. 0123).

In addition, low CD8 + values were associated with a higher T stage in the left colon ( p value = 0. 0382). Survival analysis did not demonstrate statistically significant differences between the investigated groups. Conclusions: TIL subtypes in colon cancer patients demonstrate significant variability according to the location of the primary tumor and are associated with different clinical and pathological characteristics. This exploratory study requires larger validation before TIL densities can guide therapy.

论文信息

作者
Fagarasan G、Gheban BA、Fagarasan V、Crisan D、Telecan T、Bintintan VV、Seicean RI、Caziuc A
第一作者单位
Department of Anatomy and Embriology, University of Medicine and Pharmacy Iuliu Hatieganu, 400006 Cluj Napoca, Romania.Italy
通讯作者单位
Department of Surgery, University First Surgical Clinic, County Emergency Clinical Hospital, University of Medicine and Pharmacy Iuliu Hatieganu, 400006 Cluj Napoca, Romania.Italy
期刊
Biomedicines2025 Nov 23
原文标识
PubMed 41462871 · DOI 10.3390/biomedicines13122856