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.
Oncoimmunology. 2016 Feb 18*** epublish ***
Caroline Laheurte, Jeanne Galaine, Laurent Beziaud, Magalie Dosset, Jerome Kerzerho, Claire Jacquemard, Béatrice Gaugler, Christophe Ferrand, Anne Dormoy, François Aubin, Pascale Jacoulet, Virginie Westeel, Christophe Borg, Eric Tartour, Yann Godet, Bernard Maillère, Olivier Adotévi
INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France., CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Labex LERMIT, Labex VRI , Gif Sur Yvette, France., EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431 , Besançon, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France., EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431 , Besançon, France., Department of Dermatology, University Hospital of Besançon, EA3181, SFR4234 , Besançon cedex, France., Department of Pneumology, University Hospital of Besançon , Besançon cedex, France., Department of Pneumology, University Hospital of Besançon , Besançon cedex, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France; Department of Medical Oncology, University Hospital of Besançon, Besançon cedex, France., INSERM, UMR970, Hôpital Européen Georges Pompidou, Paris, France, Department of Biological Immunology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France, University Paris Descartes , Sorbonne Paris Cité , Paris, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France., CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Labex LERMIT, Labex VRI , Gif Sur Yvette, France., INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France; Department of Medical Oncology, University Hospital of Besançon, Besançon cedex, France.