Title |
Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function
|
---|---|
Published in |
Cell Research, July 2017
|
DOI | 10.1038/cr.2017.90 |
Pubmed ID | |
Authors |
Young-hee Lee, Natalia Martin-Orozco, Peilin Zheng, Jing Li, Peng Zhang, Haidong Tan, Hyun Jung Park, Mira Jeong, Seon Hee Chang, Byung-Seok Kim, Wei Xiong, Wenjuan Zang, Li Guo, Yang Liu, Zhong-jun Dong, Willem W Overwijk, Patrick Hwu, Qing Yi, Larry Kwak, Zhiying Yang, Tak W Mak, Wei Li, Laszlo G Radvanyi, Ling Ni, Dongfang Liu, Chen Dong |
Abstract |
The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity. Expression of B7-H3 was found in multiple tumor lines, tumor-infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple tumors, which depended on NK and CD8(+) T cells. With a putative receptor expressed by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency resulted in increased cytotoxic lymphocyte function in tumor-bearing mice. Combining blockades of B7-H3 and PD-1 resulted in further enhanced therapeutic control of late-stage tumors. Taken together, our results indicate that the B7-H3 checkpoint may serve as a novel target for immunotherapy against cancer.Cell Research advance online publication 7 July 2017; doi:10.1038/cr.2017.90. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 30% |
United Kingdom | 1 | 10% |
Unknown | 6 | 60% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 7 | 70% |
Science communicators (journalists, bloggers, editors) | 3 | 30% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 207 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 40 | 19% |
Student > Bachelor | 25 | 12% |
Student > Ph. D. Student | 22 | 11% |
Student > Master | 20 | 10% |
Other | 14 | 7% |
Other | 18 | 9% |
Unknown | 68 | 33% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 37 | 18% |
Medicine and Dentistry | 34 | 16% |
Immunology and Microbiology | 25 | 12% |
Agricultural and Biological Sciences | 17 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 2% |
Other | 14 | 7% |
Unknown | 75 | 36% |