Student and Faculty Publications
Publication Date
1-1-2023
Journal
OncoImmunology
Abstract
BACKGROUND: 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.
METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (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.
RESULTS: 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.
CONCLUSIONS: Exclusion in T exhaustion cells at play across the lungs of patients with NSCLC may potentially be the mechanism for lung cancer occurrence.
Keywords
Humans, B7-H1 Antigen, Leukocytes, Mononuclear, CD8-Positive T-Lymphocytes, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Lung, Receptors, Antigen, T-Cell, IHC, NSCLC, T cell repertoire
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Immunology Commons, Oncology Commons
Comments
Supplementary Materials
Data Availability Statement
PMID: 37876834