Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, P. R. China.
Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital of Central South University, Changsha, China.
Oncoimmunology. 2023 Oct 20;12(1):2233399. doi: 10.1080/2162402X.2023.2233399. eCollection 2023.
A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients.
Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (<1 cm from tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed using immunohistochemical staining, and genomic features were derived by targeted sequencing of 1,021 cancer-related genes. Multiplex immunohistochemistry against PD-1, CTLA4, LAG3, and TIM3 was performed on four patients to assess T cell exhaustion.
Our study reveals a decreasing gradient in TIL Tumor Infiltrating Lymphocytes homology with tumor edge, adjacent lungs, and peripheral blood but no discernible distance-associated patterns of T cell trafficking within the adjacent lung itself. Furthermore, we show a decrease in pathogen-specific TCRs in regions with high T cell clonality and PD-L1 expression.
Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.
为了提高免疫疗法治疗肺癌患者的疗效并最大程度降低毒性，需要更好地了解肺癌中的 T 细胞及其在肿瘤相邻肺组织和外周血中的分布情况。
本研究对 20 名早期非小细胞肺癌患者的 136 个样本进行了 CDR3βTCR 测序，包括外周血单核细胞、肿瘤、肿瘤边缘（距离肿瘤<1cm）以及距离肿瘤 1cm、2cm、5cm 和 10cm 的相邻肺组织，以深入了解非小细胞肺癌患者肺部 T 细胞的空间异质性。采用免疫组织化学染色评估 PD-L1、CD4 和 CD8 的表达情况，并通过靶向测序 1021 个癌症相关基因获得基因组特征。对 4 名患者进行了针对 PD-1、CTLA4、LAG3 和 TIM3 的多重免疫组化分析，以评估 T 细胞耗竭情况。
我们的研究揭示了 TIL（肿瘤浸润淋巴细胞）与肿瘤边缘、相邻肺组织和外周血之间的同源性呈逐渐降低的梯度，但在相邻肺组织内部没有明显的与距离相关的 T 细胞迁移模式。此外，我们发现高 T 细胞克隆性和 PD-L1 表达区域的病原体特异性 TCR 减少。
在非小细胞肺癌患者的肺部中，T 细胞衰竭细胞的排除可能是肺癌发生的机制。
