{Reference Type}: Journal Article
{Title}: Spatial heterogeneity of T cell repertoire across NSCLC tumors, tumor edges, adjacent and distant lung tissues.
{Author}: Hu Q;Frank ML;Gao Y;Ji L;Peng M;Chen C;Wang B;Hu Y;Wu Z;Li J;Shu L;He Q;Zhang Y;Xia X;Zhang J;Yi X;Reuben A;Yu F;
{Journal}: Oncoimmunology
{Volume}: 12
{Issue}: 1
{Year}: 2023
暂无{DOI}: 10.1080/2162402X.2023.2233399
{Abstract}: <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.