B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells

Huimin Lu; Tongguo Shi; Mingyuan Wang; Xiaomi Li; Yanzheng Gu; Xueguang Zhang; Guangbo Zhang; Weichang Chen

doi:10.1080/2162402X.2020.1748991

B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells

Oncoimmunology. 2020 Apr 14;9(1):1748991. doi: 10.1080/2162402X.2020.1748991. eCollection 2020.

Authors

Huimin Lu^{1

2

3}, Tongguo Shi^{2

3

4}, Mingyuan Wang⁵, Xiaomi Li¹, Yanzheng Gu^{2

3

4}, Xueguang Zhang^{2

3

4}, Guangbo Zhang^{2

3

4}, Weichang Chen^{1

2

3

4}

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Jiangsu Institute of Clinical Immunology, the First Affiliated Hospital of Soochow University, Suzhou, China.
³ Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China.
⁴ Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
⁵ Suzhou Red Cross Blood Center, Suzhou, China.

Abstract

The immunoregulatory protein B7-H3, a member of the B7 family, has been confirmed to be highly expressed in colon cancer. However, the exact influence of B7-H3 on the features and antitumor ability of γδT cells in colon cancer remains unknown. In the present study, we investigated that the proportions of B7-H3⁺ γδT cells were distinctly increased in the peripheral blood and tumor tissues of colon cancer patients. B7-H3 blockade or knockdown promoted proliferation, inhibited cell apoptosis and induced the expression of activation markers (CD25 and CD69) on Vδ2 T cells. In contrast, treatment with the B7-H3 agonist 4H7 had the opposite effect. Furthermore, B7-H3 suppressed IFN-γ expression by inhibiting T-bet in Vδ2 T cells. Moreover, B7-H3 mediated the inhibition of Vδ2 T cell cytotoxicity via the downregulation of IFN-γ and perforin/granzyme B expression. More importantly, blocking the B7-H3 function significantly enhanced the cytotoxicity of Vδ2 T cells against colon cancer cells in vivo. Therefore, the inhibition or blockade of B7-H3 is a potential immunotherapeutic approach for colon cancer.

Keywords: B7-H3; Colon cancer; IFN-γ; perforin/granzyme pathway; γδT cells.

Publication types

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

MeSH terms

B7-H1 Antigen* / antagonists & inhibitors
B7-H1 Antigen* / immunology
Case-Control Studies
Colonic Neoplasms* / drug therapy
Humans
Interferon-gamma* / antagonists & inhibitors
Interferon-gamma* / immunology
Receptors, Antigen, T-Cell, gamma-delta / immunology
T-Lymphocytes* / immunology

Substances

B7-H1 Antigen
CD274 protein, human
Receptors, Antigen, T-Cell, gamma-delta
Interferon-gamma

Grants and funding

This study was supported by the National Natural Science Foundation of China (81672372, 81802843, 81372276); Colleges and Universities Natural Science Research Project of Jiangsu Province (18KJB320023, 17KJA310004); Suzhou Science & Technology plan project (SYS2019035).