400P - Combining anti-angiogenesis and immunotherapy enhances antitumor effect in lung cancer

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cancer Immunology and Immunotherapy
Presenter Sha Zhao
Citation Annals of Oncology (2016) 27 (suppl_9): ix123-ix125. 10.1093/annonc/mdw588
Authors S. Zhao1, T. Jiang2, X. Li1, C. Zhou3
  • 1Medical Oncology, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN
  • 2Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, 200433 - Shanghai/CN
  • 3Department Of Oncology, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN

Abstract

Background

Increasing studies have shown that anti-angiogenesis are furnishing demonstrable therapeutic effect on lung cancer, but the treatment benefit is limit in clinic. Blockade of VEGF/VEGFR2 pathway can not only induce anti-vascular effect, but also remodel the immunosuppressive tumor microenvironment probably due to promoting suppressive cells infiltration and enhancing PD-L1 expression, resulting in impairing antitumor immunity. Thus, the current study aimed to investigate whether combining anti-angiogenic and anti-PD-L1 treatments can induce synergistic antitumor effect by enhancing antitumor immune response in murine lung cancer.

Methods

We evaluated the antitumor effects of anti-VEGFR2 agent (apatinib) as monotherapy or in combination with anti-PD-L1 monoclonal antibody in murine lung cancer model using Lewis lung cancer cells (LLCs). The changes of immune components in tumor and spleen were dynamically tested in different treatment groups and time points by flow cytometry and immunohistochemistry.

Results

The results showed apatinib could retard tumor growth and inhibit neovascularization via eradicating Foxp3+ regulatory T cells (Tregs) and myeloid derived suppressive cells (MDSCs) and reducing the density of microvessels in the first two weeks of treatment. On the third week of apatinib monotherapy, the number of Tregs and MDSCs increased again. Although anti-VEGFR2 treatment induced more tumor infiltrating lymphocytes (TILs), especially CD8+ T cells, infiltrating into the tumor mass than control group (P 

Conclusions

Simultaneous blockade of VEGF/VEGFR2 and PD-1/PD-L1 pathways induced synergistic anti-tumor effect in-vivo, possibly through eliminating immunosuppressive components including Tregs and MDSCs and enhance antitumor immune response.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.