Distinct prognostic value of circulating anti-telomerase CD4(+) Th1 immunity and exhausted PD-1(+)/TIM-3(+) T cells in lung cancer

BACKGROUND: Despite the critical roles of Th1-polarised CD4(+) T cells in cancer immunosurveillance, the translation of their potential to clinical use remains challenging. Here, we investigate the clinical relevance of circulating antitumor Th1 immunity in non-small cell lung cancer (NSCLC). METHODS: The circulating antitumor Th1 response was assessed by the ELISpot assay in 170 NSCLC patients using a mixture of HLA class II-restricted peptides from telomerase (TERT). Phenotyping of blood immune cells was performed by flow cytometry. RESULTS: TERT-reactive CD4 T-cell response was detected in 35% of NSCLC patients before any treatment. Functional analysis showed that these cells were effector memory and Th1 polarised capable to produce effector cytokines, such as IFN-γ, TNF-α and IL-2. The presence of anti-TERT Th1 response was inversely correlated with the level of exhausted PD-1(+)/TIM-3(+)CD4 T cells. The level of these two immune parameters differentially affected the survival, so that increased level of anti-TERT Th1 response and low rate of exhausted PD-1(+)TIM-3(+)CD4(+) T cells were associated with a better prognosis. CONCLUSIONS: Systemic anti-TERT Th1 response plays a strong antitumor protective role in NSCLC. This study underlines the potential interest of monitoring circulating antitumor Th1 response for patients’ stratification and therapy decision.