Ablation of B7-H3 but Not B7-H4 Results in Highly Increased Tumor Burden in a Murine Model of Spontaneous Prostate Cancer

Katharina Kreymborg; Stefan Haak; Rajmohan Murali; Joyce Wei; Rebecca Waitz; Georg Gasteiger; Peter A Savage; Marcel R M van den Brink; James P Allison

doi:10.1158/2326-6066.CIR-15-0100

Ablation of B7-H3 but Not B7-H4 Results in Highly Increased Tumor Burden in a Murine Model of Spontaneous Prostate Cancer

Cancer Immunol Res. 2015 Aug;3(8):849-54. doi: 10.1158/2326-6066.CIR-15-0100. Epub 2015 Jun 29.

Authors

Katharina Kreymborg¹, Stefan Haak², Rajmohan Murali³, Joyce Wei⁴, Rebecca Waitz¹, Georg Gasteiger¹, Peter A Savage⁵, Marcel R M van den Brink⁶, James P Allison⁷

Affiliations

¹ Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York.
² Columbia University Medical Center, New York, New York. Centre of Allergy and Environment (ZAUM), Technical University and Helmholtz Centre Munich, Munich, Germany.
³ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
⁴ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
⁵ Department of Pathology, University of Chicago, Chicago, Illinois.
⁶ Department of Immunology and Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
⁷ Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas. JAllison@mdanderson.org.

Abstract

The costimulatory molecules B7-H3 and B7-H4 are overexpressed in a variety of human tumors and have been hypothesized as possible biomarkers and immunotherapeutic targets. Despite this potential, the predominating uncertainty about their functional implication in tumor-host interaction hampers their evaluation as a target for cancer therapy. By means of a highly physiologic, spontaneous tumor model in mice, we establish a causal link between B7-H3 and host tumor control and found B7-H4 to be redundant.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B7 Antigens / genetics*
B7 Antigens / metabolism
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Disease Models, Animal
Gene Deletion*
Humans
Immunophenotyping
Lymphocytes, Tumor-Infiltrating / immunology
Lymphocytes, Tumor-Infiltrating / metabolism
Male
Mice
Mice, Knockout
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / immunology
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Tumor Burden
V-Set Domain-Containing T-Cell Activation Inhibitor 1 / genetics*
V-Set Domain-Containing T-Cell Activation Inhibitor 1 / metabolism

Substances

B7 Antigens
Cd276 protein, mouse
RNA, Messenger
V-Set Domain-Containing T-Cell Activation Inhibitor 1
Vtcn1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding