84P - Presence of naturally occurring anti-telomerase CD4 Th1 immunity in glioblastoma (84P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Supportive Care
Palliative and Supportive Care
Presenter Guillaume Meynard
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors G. Meynard1, L. Boullerot2, S. Belmiloudi3, M. Dosset2, C. Laheurte2, D. Guenat3, L. Rangan2, E. Lauret Marie Joseph2, C. Verlut1, Y. Godet2, S. Valmary-Degano4, I. Mihai4, X. Pivot1, E. Curtit1, O. Adotevi2
  • 1Medical Oncology, University Hospital of Besançon, 25000 - Besancon/FR
  • 2Umr1098 Inserm/efs/ubfc, University Bourgogne Franche-Comte, 25000 - Besancon/FR
  • 3Laboratory Of Cellular And Molecular Biology, University Hospital of Besançon, 25000 - Besancon/FR
  • 4Department Of Pathology, University Hospital of Besançon, 25000 - Besancon/FR

Abstract

Background

Telomerase (TERT) emerges as an attractive target for immunotherapy in glioblastoma (GBMs), the most common primary brain tumor in adults. High prevalence (∼80%) of activating mutations in TERT promoter was found in GBMs. Our aim was to analyze the spontaneous CD4 Th1 response against TERT in patients with GBMs.

Methods

Thirty-seven GBM patients were analyzed in this study. The anti-TERT Th1 response was measured by IFN-ɣ ELISPOT assay after in vitro stimulation of blood lymphocytes with Th1 epitopes derived from TERT. Peptides mixture derived from Wilms tumor 1 (WT1) was used as second model of GBM-associated tumor antigen. The recall of the antiviral response was also evaluated for each patients by IFN-ɣ ELISPOT assay. Regulatory T cell (Treg) [CD4+CD25+ CD127lowFoxP3+] and monocytic myeloid-derived suppressor cells (M-MDSC) [Lin- HLA-DR-/low CD11b+CD14+CD33+] were measured in blood by flow cytometry. TERT promoter mutations (C228T and C250T) were analyzed on brain tumor using DNA sequencing.

Results

The spontaneous anti-TERT Th1 response was detected in 43.2% (16/37) of GBM patients, and 58.1% patients had anti-WT1 Th1 response. A strong correlation was observed between these two antitumor immune responses. However, there was no correlation between the antitumor immunity and the anti-viral response detected in most patients (91%). We found that the frequency of anti-TERT Th1 response decreased in patients exhibiting high circulating level of Treg and M-MDSC. In contrast to anti-WT1 Th1 response, the anti-TERT Th1 response appeared to be positively associated with patients’ overall survival (OS). Interestingly, this association was more pronounced, but non-significant, when focusing on GBM patients exhibiting TERT promoter mutations (median OS: 33.6 vs 16.3 months, in anti-TERT Th1 responders and non-responders respectively).

Conclusions

We report the presence of spontaneous anti-TERT Th1 response in blood of patients with GBM. This response tends to increase patients’ OS suggesting its involvement in GBM immunosurveillance. These results strongly support the rational to develop immunotherapy targeting telomerase in glioblastoma.

Clinical trial identification

Legal entity responsible for the study

University Hospital Jean Minjoz of Besancon

Funding

None

Disclosure

All authors have declared no conflicts of interest.