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- Title
Distinct prognostic value of circulating anti-telomerase CD4<sup>+</sup> Th1 immunity and exhausted PD-1<sup>+</sup>/TIM-3<sup>+</sup> T cells in lung cancer.
- Authors
Laheurte, Caroline; Dosset, Magalie; Vernerey, Dewi; Boullerot, Laura; Gaugler, Béatrice; Gravelin, Eléonore; Kaulek, Vincent; Jacquin, Marion; Cuche, Laurie; Eberst, Guillaume; Jacoulet, Pascale; Fabre, Elizabeth; Le Pimpec-Barthes, Françoise; Tartour, Eric; De Carvalho Bittencourt, Marcelo; Westeel, Virginie; Adotévi, Olivier
- Abstract
<bold>Background: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
British Journal of Cancer, 2019, Vol 121, Issue 5, p405
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-019-0531-5