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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Antigens, Surface*
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Apoptosis Regulatory Proteins
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology*
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B7-1 Antigen / metabolism
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B7-H1 Antigen
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Blood Proteins*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CHO Cells
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Cricetinae
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Cytotoxicity, Immunologic
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Membrane Glycoproteins
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Neoplasm Transplantation
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Neoplasms, Experimental / immunology*
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Peptides*
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Programmed Cell Death 1 Ligand 2 Protein
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Programmed Cell Death 1 Receptor
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Proteins / immunology*
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Proteins / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism
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Spleen / cytology
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Spleen / immunology
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T-Lymphocytes, Cytotoxic / immunology
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Transgenes
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Transplantation Chimera
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Tumor Cells, Cultured
Substances
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Antigens, Neoplasm
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Antigens, Surface
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Apoptosis Regulatory Proteins
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B7-1 Antigen
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B7-H1 Antigen
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Blood Proteins
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Cd274 protein, mouse
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Membrane Glycoproteins
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Pdcd1 protein, mouse
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Pdcd1lg2 protein, mouse
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Peptides
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Programmed Cell Death 1 Ligand 2 Protein
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Programmed Cell Death 1 Receptor
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Proteins
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Receptors, Antigen, T-Cell