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

• Published in: British journal of cancer 2019-08, Vol.121 (5), p.405-416
• Main 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
• Format: Article
• Language: English
• Subjects: 631/250/2520; 692/4028/67/1612/1350; 692/53/2422; Adaptive immunology; Aged; Antitumor activity; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Carcinoma, Non-Small-Cell Lung - immunology; CD4 antigen; Cytokines - immunology; Drug Resistance; Effector cells; Enzyme-linked immunosorbent assay; Epidemiology; Female; Flow cytometry; Functional analysis; Hepatitis A Virus Cellular Receptor 2 - immunology; Histocompatibility antigen HLA; Human health and pathology; Humans; Immunity; Immunological memory; Immunology; Immunosurveillance; In Vitro Techniques; Interleukin 2; Life Sciences; Lung cancer; Lung Neoplasms - immunology; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Middle Aged; Molecular Medicine; Non-small cell lung carcinoma; Oncology; Patients; PD-1 protein; Peptides; Phenotyping; Prognosis; Programmed Cell Death 1 Receptor - immunology; Pulmonology and respiratory tract; Survival Rate; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; Telomerase; Telomerase - immunology; Th1 Cells - immunology; Tumor necrosis factor-α; γ-Interferon
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-019-0531-5

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.