title: Immunoprevalence and magnitude of HLA-DP4 versus HLA-DR-restricted spontaneous CD4(+) Th1 responses against telomerase in cancer patients.
abstract: 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.
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Laheurte
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Galaine
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Beziaud
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Dosset
authors.affiliation: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Labex LERMIT, Labex VRI , Gif Sur Yvette, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Kerzerho
authors.affiliation: EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431 , Besançon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Jacquemard
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gaugler
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.affiliation: EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431 , Besançon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dormoy
authors.affiliation: Department of Dermatology, University Hospital of Besançon, EA3181, SFR4234 , Besançon cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Aubin
authors.affiliation: Department of Pneumology, University Hospital of Besançon , Besançon cedex, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Jacoulet
authors.affiliation: Department of Pneumology, University Hospital of Besançon , Besançon cedex, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
authors.affiliation: 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.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Godet
authors.affiliation: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Labex LERMIT, Labex VRI , Gif Sur Yvette, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillère
authors.affiliation: INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France; Department of Medical Oncology, University Hospital of Besançon, Besançon cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Adotévi
keywords: CD4+ Th1 cells; HLA-DP4; HLA-DR; immunomonitoring; telomerase