Wu Jiajuan, Guo Shiying, Lv Leilei, Zhai Jiawei, Shen Yu, Chen Cheng, Qu Qiuxia
Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Respiratory and Critical Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Zhongguo Fei Ai Za Zhi. 2024 Dec 20;27(12):903-910. doi: 10.3779/j.issn.1009-3419.2024.102.46.
One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment.
Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed.
The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)].
In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
免疫检查点抑制剂是非小细胞肺癌（NSCLC）最重要的治疗方式之一。然而，一小部分患者对这些疗法反应不佳，这凸显了识别免疫治疗中重要的CD8 + T细胞亚群并创建可靠生物标志物的重要性。本研究的目的是通过检测TIM3 + CD8 + T细胞在NSCLC肿瘤微环境各个区域的表达，评估其作为新生物标志物的潜在效用。
基于活检技术，从NSCLC患者获取肿瘤组织样本，并分为肿瘤中心和非中心区域。使用流式细胞术，检测TIM3 + CD8 + T细胞的浸润情况以及这些细胞上程序性细胞死亡蛋白1（PD - 1）的表面表达，并评估它们与免疫治疗效果的相关性。
与肿瘤非中心区域相比，肿瘤组织的中心区域TIM3 + CD8 + T淋巴细胞浸润明显更多（P < 0.0001）。在肿瘤直径≥3 cm或<3 cm的两个亚组中均发现了这种模式（P < 0.01）。与TIM3 - CD8 + T细胞相比，TIM3 + CD8 + T细胞显示出更高水平的PD - 1（P < 0.001），更多的PD - 1 + TIM3 + CD8 + T细胞侵入非中心区域（P < 0.01）。与无反应者相比，免疫治疗的临床反应者在肿瘤非中心区域的TIM3 + CD8 + T细胞浸润水平明显更低，较低水平与更好的临床结果相关（P < 0.01），而在肿瘤中心区域未发现相关性（P > 0.05）。根据受试者工作特征（ROC）曲线分析，肿瘤非中心区域的TIM3 + CD8 + T细胞预测免疫治疗效果的曲线下面积（AUC）为0.9375，明显高于肿瘤中心区域的TIM3 + CD8 + T细胞和程序性细胞死亡配体1（PD - L1）[肿瘤比例评分（TPS）]。
在NSCLC的肿瘤微环境中，TIM3 + CD8 + T细胞呈现区域分布模式。该细胞群体在肿瘤微环境非中心区域的表达可能是预测免疫治疗效果的生物标志物。
