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Oncoimmunology. 2016 Feb 18;5(5):e1137416. doi: 10.1080/2162402X.2015.1137416. eCollection 2016 May.

Immunoprevalence and magnitude of HLA-DP4 versus HLA-DR-restricted spontaneous CD4(+) Th1 responses against telomerase in cancer patients.

Author information

1
INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France.
2
INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
3
CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Labex LERMIT, Labex VRI , Gif Sur Yvette, France.
4
EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431 , Besançon, France.
5
INSERM, UMR1098, LabEx LipSTIC, Besançon, France; EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, INSERM CIC1431, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France.
6
Department of Dermatology, University Hospital of Besançon, EA3181, SFR4234 , Besançon cedex, France.
7
Department of Pneumology, University Hospital of Besançon , Besançon cedex, France.
8
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.
9
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.
10
INSERM, UMR1098, LabEx LipSTIC, Besançon, France; Univ. Bourgogne Franche-Comté, UMR1098, Besançon, France; Department of Medical Oncology, University Hospital of Besançon, Besançon cedex, France.

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.

KEYWORDS:

CD4+ Th1 cells; HLA-DP4; HLA-DR; immunomonitoring; telomerase

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