823P - Sunitinib pretreatment does not impair tumor infiltrating lymphocyte (TIL) expansion but reduces intratumoral content of myeloid-derived suppressor...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Translational Research
Presenter Christian Blank
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors C. Blank1, A. Guislain2, J. Gadiot2, A. Kaiser2, K. Jordanova3, A. Broeks3, H.H. van Boven3, T. De Gruijl4, J.B.A.G. Haanen1, A. Bex5
  • 1Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 2Div. Immunology, The Netherlands Cancer Institute, Amsterdam/NL
  • 3Dept. Pathology, The Netherlands Cancer Institute, Amsterdam/NL
  • 4Div. Immunology, VU Medical Center, Amsterdam/NL
  • 5Dept. Urology, The Netherlands Cancer Institute, Amsterdam/NL

Abstract

Aim

Targeted therapy (TT), with e.g. suntinib, pazopanib or everolimus, has improved treatment outcome for metastasized renal cell carcinoma patients, but despite considerable effort in sequential or combined modalities, durable remissions do not occur. Immunotherapeutic approaches, like cytokine therapy with interleukin (IL)-2, T cell checkpoint inhibition (TcCB) or adoptive T cell therapies (ACT), can achieve long-term benefit or even cure. This raises the question of whether combining TT with TcCB or ACT could improve patients' outcomes. However, based on pre-clinical in vitro tests, sunitinib is thought to hamper T cell functions and possible increases intratumor myeloid-derived suppressor cells (MDSC) content.

Methods

We therefore compared renal cell carcinoma (RCC) tumor material from patients either pretreated with sunitinib or not (sunitinib-naïve) for ability to grow TIL form these tissues and for their content of regulatory T cells (Treg) and MDSC.

Results

We found no impaired TIL expansion after sunitinib treatment, but wel reduced intratumoral MDSC content, while the amount of intratumoral Treg was not altered.

Conclusions

Suntitinb is thus a good combination partner for ACT and/or TcCB, which could be extended by adding a Treg-altering agent.

Disclosure

C. Blank: Advisory role for Roche, GSK, MSD, BMS, and Novartis. Research grant form Novartis;

J.B.A.G. Haanen: Advisory role for Roche and GSK and research grant from GSK. All other authors have declared no conflicts of interest.