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B7DC/PDL2 Promotes Tumor Immunity by a PD-1–independent Mechanism

Xingluo Liu¹, Jian Xin Gao¹, Jing Wen¹, Lijie Yin¹, Ou Li¹, Tao Zuo¹, Thomas F. Gajewski², Yang-Xin Fu², Pan Zheng¹ and Yang Liu¹

¹ Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210
² Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637

Address correspondence to Yang Liu, Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210. Phone: 614-292-3054; Fax: 614-688-8152; E-mail: liu-3{at}medctr.osu.edu

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.

Key Words: tumor immunity • costimulatory molecules • cytolytic T lymphocytes

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