%0 Journal Article
%T Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues.
%A Hu Q
%A Frank ML
%A Gao Y
%A Ji L
%A Peng M
%A Chen C
%A Wang B
%A Hu Y
%A Wu Z
%A Li J
%A Shu L
%A He Q
%A Zhang Y
%A Xia X
%A Zhang J
%A Yi X
%A Reuben A
%A Yu F
%J Oncoimmunology
%V 12
%N 1
%D 2023
%M 37876834
暂无%R 10.1080/2162402X.2023.2233399
%X <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.