PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.
摘要：
■需要更好地了解肺癌中的T细胞及其在肿瘤旁肺和外周血中的分布，以提高疗效并最大程度地减少免疫治疗对肺癌患者的毒性。
■这里，我们对来自20例早期NSCLC患者的136个样本进行了CDR3βTCR测序，包括外周血单个核细胞，肿瘤，肿瘤边缘（距离肿瘤<1厘米），以及邻近的肺1厘米，2厘米,5cm,距离肿瘤10厘米，以深入了解非小细胞肺癌患者肺部T细胞的空间异质性。使用免疫组织化学染色评估PD-L1，CD4和CD8表达，基因组特征是通过对1,021个癌症相关基因的靶向测序得出的。对四名患者进行针对PD-1，CTLA4，LAG3和TIM3的多重免疫组织化学，以评估T细胞耗竭。
■我们的研究揭示了TIL肿瘤浸润淋巴细胞与肿瘤边缘的同源性梯度下降，邻近的肺，和外周血，但没有明显的距离相关的T细胞运输模式在相邻的肺本身。此外，我们显示了在具有高T细胞克隆性和PD-L1表达的区域中病原体特异性TCR的减少。
■在非小细胞肺癌患者的肺中排斥T细胞可能是肺癌发生的潜在机制。
■这里，我们对来自20例早期NSCLC患者的136个样本进行了CDR3βTCR测序，包括外周血单个核细胞，肿瘤，肿瘤边缘（距离肿瘤<1厘米），以及邻近的肺1厘米，2厘米,5cm,距离肿瘤10厘米，以深入了解非小细胞肺癌患者肺部T细胞的空间异质性。使用免疫组织化学染色评估PD-L1，CD4和CD8表达，基因组特征是通过对1,021个癌症相关基因的靶向测序得出的。对四名患者进行针对PD-1，CTLA4，LAG3和TIM3的多重免疫组织化学，以评估T细胞耗竭。
■我们的研究揭示了TIL肿瘤浸润淋巴细胞与肿瘤边缘的同源性梯度下降，邻近的肺，和外周血，但没有明显的距离相关的T细胞运输模式在相邻的肺本身。此外，我们显示了在具有高T细胞克隆性和PD-L1表达的区域中病原体特异性TCR的减少。
■在非小细胞肺癌患者的肺中排斥T细胞可能是肺癌发生的潜在机制。
