期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14754
关键词
-
资金
- NIH [P01CA132714, R01CA155925, P30CA047904]
- New Era Cap Company
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector Tcells and induces PD-L1 expression on both cancer and immune cells in the tumour. The dual therapy reduces PD-L1(+) cells and facilitates non-redundant tumour infiltration of effector CD8(+), CD4(+) T cells, with increased IFN-gamma, ICOS, granzyme B and perforin expression. Furthermore, the treatment reduces the virus-induced PD-L1(+) DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1(+) CD8(+) T cells, leading to reduced tumour burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients.
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