1081P - The efficacy of everolimus relies on a modulation of adaptative anti tumor T cell immunity

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Therapy
Presenter Olivier Adotévi
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors O. Adotévi1, L. Mansi1, L. Beziaud1, P. Ravel2, E. Lauret Marie-Joseph1, C. Laheurte1, L. Rangan1, T. Maurina1, G. Mouillet1, T. Nguyen Tan Hon1, E. Curtit1, X. Pivot1, Y. Godet1, C. Borg1, A. Thiery-Vuillemin1
  • 1Medical Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 2Biostatistic, ICM Regional Cancer Institute of Montpellier, Montpellier/FR

Abstract

Background

The rapalogs everolimus that inhibit mTOR signaling are used as anti-proliferative drugs in metastatic renal cell carcinoma (mRCC). The influence of immune modulation mediated by everolimus on its antitumor efficacy is poorly investigated.

Methods

We performed a prospective immunomonitoring study in 23 mRCC patients treated with everolimus.

Results

Study showed that everolimus promoted high expansion of FoxP3+Helios+Ki67+ regulatory CD4 T cells (Tregs). Everolimus exposure strongly enhanced the suppressive functions of patients' Tregs. Paradoxically, a concurrent activation of tumor-specific Th1 immunity also occurred during everolimus treatment. Interestingly, an early change of the Tregs/antitumor Th1 balance can differentially shapes the treatment efficacy. Thus, patients presenting a shift towards Tregs decrease and high expansion of antitumor Th1 response had a better survival (PFS: 13.2 months vs 4.1 months P = 0.02). At the time of disease progression upon everolimus treatment, the majority of mRCC patients totally lost the anti-tumor Th1 response in favor to a marked increase of circulating Tregs.

Conclusions

Altogether, our results describe for the first time a dual impact of host adaptive antitumor T cell immunity on the clinical effectiveness of everolimus. So there is a strong rational to combine everolimus with Tregs or immune checkpoint blockade to shift host immune responses toward protective antitumor immunity.

Clinical trial identification

Legal entity responsible for the study

University Hospital of Besançon France

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.