1. Function of Human Tumor-Infiltrating Lymphocytes in Early-Stage Non–Small Cell Lung Cancer
- Author
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Edmund K. Moon, Jeffrey C. Thompson, Sunil Singhal, Abhishek Rao, Wei-Ting Hwang, Leslie A. Litzky, Marina Martinez, Astero Klampatsa, Jason E Standalick, Edward Cantu, Shaun O'Brien, Evgeniy Eruslanov, Steven M. Albelda, and Soyeon Kim
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Immunology ,Gene Expression ,Eomesodermin ,chemical and pharmacologic phenomena ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocyte Activation ,Article ,Immunophenotyping ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,TIGIT ,Carcinoma, Non-Small-Cell Lung ,Cause of Death ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,Lung cancer ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Cancer ,hemic and immune systems ,Immunotherapy ,Middle Aged ,Prognosis ,medicine.disease ,030104 developmental biology ,Cytokine ,Biological Variation, Population ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Immunologic Memory ,CD8 - Abstract
Cancer progression is marked by dysfunctional tumor-infiltrating lymphocytes (TIL) with high inhibitory receptor (IR) expression. Because IR blockade has led to clinical responses in some patients with non–small cell lung cancer (NSCLC), we investigated how IRs influenced CD8+ TIL function from freshly digested early-stage NSCLC tissues using a killing assay and intracellular cytokine staining after in vitro T-cell restimulation. Early-stage lung cancer TIL function was heterogeneous with only about one third of patients showing decrements in cytokine production and lytic function. TIL hypofunction did not correlate with clinical factors, coexisting immune cells (macrophages, neutrophils, or CD4+ T regulatory cells), nor with PD-1, TIGIT, TIM-3, CD39, or CTLA-4 expression. Instead, we found that the presence of the integrin αeβ7 (CD103), characteristic of tissue-resident memory cells (TRM), was positively associated with cytokine production, whereas expression of the transcription factor Eomesodermin (Eomes) was negatively associated with TIL function. These data suggest that the functionality of CD8+ TILs from early-stage NSCLCs may be influenced by competition between an antitumor CD103+ TRM program and an exhaustion program marked by Eomes expression. Understanding the mechanisms of T-cell function in the progression of lung cancer may have clinical implications for immunotherapy.
- Published
- 2019
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