Apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression

•Apatinib treatment increased PD-L1 expression in various colon cancer cells.•Apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells.•The combination of apatinib with anti-PD-1 significantly inhibited colon cancer growth in mice. Increasing studies confirm that anti-angioge...

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Veröffentlicht in:International immunopharmacology 2020-11, Vol.88, p.106858-106858, Article 106858
Hauptverfasser: Cai, Xiaomin, Wei, Bin, Li, Lele, Chen, Xiaofeng, Liu, Wen, Cui, Jian, Lin, Yumeng, Sun, Yang, Xu, Qiang, Guo, Wenjie, Gu, Yanhong
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Sprache:eng
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Zusammenfassung:•Apatinib treatment increased PD-L1 expression in various colon cancer cells.•Apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells.•The combination of apatinib with anti-PD-1 significantly inhibited colon cancer growth in mice. Increasing studies confirm that anti-angiogenesis can increase the effectiveness of immunotherapy. In this study, we found that an angiogenesis inhibitor apatinib enhanced anti-PD-1 therapy for colon cancer in mice via promoting PD-L1 expression. Apatinib treatment upregulated PD-L1 expression in various colon cancer cells both at the mRNA and protein levels. Further, apatinib-treated cancer cells hampered activation and IFN-γ secretion of T cells in the co-culture system, which was reversed by the anti-PD-1 antibody. Based on this, the combination of apatinib with anti-PD-1 on colon cancer growth in mice was examined. The combination treatment showed more significant inhibition on the growth of transplanted tumors in mice than single-drug treatment. Overall, our study here showed the enhancement of anti-PD-1 antitumor efficacy in a syngeneic mouse model (CT-26 cells in Balb/c) by the angiogenesis inhibitor apatinib via upregulating PD-L1 expression as well as angiogenesis inhibition, which may provide a rationale for the combination of apatinib and anti-PD-1 antibody for colorectal cancer treatment in the clinic.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2020.106858