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S. Zhao
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OA11 - Angiogenesis in Advanced Lung Cancer (ID 387)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:L.M. Montuenga, J. Heymach
- Coordinates: 12/06/2016, 11:00 - 12:30, Stolz 2
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OA11.07 - Combining Anti-Angiogenesis and Immunotherapy Enhances Antitumor Effect by Promoting Immune Response in Lung Cancer (ID 4985)
11:00 - 12:30 | Author(s): S. Zhao
- Abstract
- Presentation
Background:
Increasing studies have shown that anti-angiogenic therapy targeting VEGF/VEGFR2 axis are furnishing demonstrable therapeutic effect on lung cancer，but the treatment benefit is transitory in clinic, generally followed by restoration of tumor growth and disease progression. 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. Therefore, 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 a 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 that VEGF/VEGFR2 blockade could retard tumor growth and inhibit tumor 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 Foxp3[+ ]Tregs and MDSCs had increased again. Although VEGF/VEGFR2 blockade induced more tumor infiltrating lymphocytes (TILs), especially CD8[+] T cells, infiltrating into the tumor mass than control group (P < 0.01), the expression of PD-1 and PD-L1was also significantly upregulated than that control group (P < 0.01). Compared to apatinib monotherapy, combining treatment demonstrated that anti-VEGFR2 plus anti-PD-L1 therapy could significantly inhibit tumor growth (P < 0.01) by persistently eliminating Foxp3[+ ]Tregs and MDSCs. Furthermore, combining anti-VEGFR2 and anti-PD-L1 therapy could not only dramatically increase TILs infiltration, especially CD8[+] T cells, but also significantly reduce the expression of PD-1 and PD-L1.
Conclusion:
Simultaneous blockade of VEGF/VEGFR2 and PD-1/PD-L1 pathways induced a synergistic anti-tumor effect in-vivo, possibly through eliminating immunosuppressive components including Tregs and MDSCs and enhance antitumor immune response.
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