Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues

Background A better understanding of the T cells in lung cancer and their distribution across tumor-adjacent lungs and the peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients. Methods Here, we performed CDR3β TCR sequencing of 143 samples from 21 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumor, tumor edges (<1cm from tumor), as well as adjacent lungs 1cm, 2cm, 5cm, and 10cm 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 by immunohistochemical staining and genomic features were derived by targeted sequencing of 1,021 cancer related genes. Results Our study reveals a decreasing gradient in TIL homology with the 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. Conclusions The exclusion in T cells at play across the lungs of patients with NSCLC may be potentially the mechanism for lung cancer occurrence.