Immunoprevalence and magnitude of HLA-DP4 versus HLA-DR-restricted spontaneous CD4(+) Th1 responses against telomerase in cancer patients.
Fiche publication
Date publication
mai 2016
Journal
Oncoimmunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr AUBIN François, Pr BORG Christophe, Dr FERRAND Christophe, Dr GODET Yann, Pr WESTEEL Virginie, Mme LAHEURTE Caroline, Dr GALAINE Jeanne
Tous les auteurs :
Laheurte C, Galaine J, Beziaud L, Dosset M, Kerzerho J, Jacquemard C, Gaugler B, Ferrand C, Dormoy A, Aubin F, Jacoulet P, Westeel V, Borg C, Tartour E, Godet Y, Maillère B, Adotévi O
Lien Pubmed
Résumé
Cumulative evidence supports that CD4(+) Th1 cells play a key role in antitumor immunity. We previously reported the presence of spontaneous HLA-DR-restricted CD4(+) Th1 responses against telomerase reverse transcriptase (TERT) in various cancers by using promiscuous HLA-DR epitopes. Here, we described novel highly immunogenic HLA-DP4-binding epitopes from TERT named TERT541-555, TERT573-587, TERT613-627 and TERT911-925 and addressed the question about the immunoprevalence and magnitude of the naturally occurring antitumor CD4(+) T cell responses restricted by HLA-DP4 or HLA-DR, the two most common HLA class II. Direct comparative study of spontaneous anti-TERT CD4(+) T cell responses in a cohort of 87 lung cancer patients showed that HLA-DP4 and HLA-DR sustained specific Th1 responses in 10.1% and 25.2% of cancer patients respectively (p = 0.01). The magnitude of the HLA-DR-restricted responses was two to three times significantly higher than HLA-DP one (p = 0.005). Similar results were found in other cancers such as melanoma, breast cancer, renal cell carcinoma and colon cancer. Thus, our results describe for the first time in a large cohort of cancer patients a high immunoprevalence of HLA-DR-restricted spontaneous anti-TERT Th1 immunity compared to HLA-DP restriction. These results provide a new tool for comprehensive monitoring of antitumor CD4(+) Th1 response in various cancers.
Mots clés
CD4+ Th1 cells, HLA-DP4, HLA-DR, immunomonitoring, telomerase
Référence
Oncoimmunology. 2016 May;5(5):e1137416