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B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism
Xingluo Liu1, Jian Xin Gao, Jing Wen
1Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.
Abstract:
B7H1 (PDL1) and B7DC (PDL2) are two new members of the B7 family that can interact with PD-1, a putative negative regulator for immune function. Recent studies have provided evidence for inhibitory functions of both members via PD-1. Meanwhile, compelling evidence exists for costimulatory function of both members. Here we demonstrate that expression of B7DC on the tumor cells promotes CD8 T cell-mediated rejection of tumor cells, at both the induction and effector phase of antitumor immunity. Moreover, B7DC binds to PD-1(-/-) cells and enhances T cell killing in a PD-1-independent mechanism. Our results demonstrate a novel pathway for B7DC to promote tumor immunity and may reconcile the apparently contradictory findings on the function of B7DC.
Insights
B7DC (PDL2) costimulates CD8 T cell immunity against tumors. This immune costimulation occurs via a novel pathway, independent of PD-1, and promotes tumor rejection.
Area of Science:
- Immunology
- Cancer Immunology
- Molecular Biology
Background:
- B7H1 (PDL1) and B7DC (PDL2) are B7 family members interacting with PD-1, a negative immune regulator.
- Previous studies suggest both inhibitory and costimulatory roles for B7H1 and B7DC via PD-1.
- Contradictory findings exist regarding the precise functions of B7DC in antitumor immunity.
Purpose of the Study:
- To investigate the role of B7DC in CD8 T cell-mediated antitumor immunity.
- To elucidate the mechanism by which B7DC influences tumor rejection.
- To reconcile conflicting data on B7DC function.
Main Methods:
- Tumor cell expression of B7DC was analyzed.
- CD8 T cell responses were assessed in the presence of B7DC.
- Tumor rejection was evaluated in models involving B7DC and PD-1 knockout cells.
Main Results:
- B7DC expression on tumor cells enhances CD8 T cell-mediated tumor rejection.
- B7DC promotes both the induction and effector phases of antitumor immunity.
- B7DC enhances T cell killing through a PD-1-independent mechanism.
Conclusions:
- B7DC has a novel costimulatory role in promoting tumor immunity.
- B7DC facilitates tumor rejection via a PD-1-independent pathway.
- These findings reconcile previous contradictory observations on B7DC function.