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Function of Human Tumor-Infiltrating Lymphocytes in Early-Stage Non-Small Cell Lung Cancer
Ist Teil von
Cancer immunology research, 2019-06, Vol.7 (6), p.896-909
Ort / Verlag
United States
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
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
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 α
β
(CD103), characteristic of tissue-resident memory cells (T
), 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
T
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.