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Open Access 01-02-2020 | Original Article

B7H4 expression in tumor cells impairs CD8 T cell responses and tumor immunity

Authors: Linlin Zhou, Mei Ruan, Ying Liu, Yanyang Zhu, Deqiang Fu, Kunlin Wu, Qiuyu Zhang

Published in: Cancer Immunology, Immunotherapy | Issue 2/2020

Abstract

B7 homolog 4 (B7H4) is considered a negative regulator of immune responses, but the immunoregulatory role of B7H4 in the tumor microenvironment is not clear. Here, we assessed B7H4 expression cell types in human breast cancer tissues and addressed its potential mechanisms in the CD8 T cell immune response. The results from flow cytometry and immunohistochemistry demonstrated that B7H4 was highly expressed in 26 out of 30 (86.7%) breast invasive ductal carcinomas, and B7H4 surface expression on tumor cells was inversely correlated with CD8 T lymphocytes infiltration (p < 0.0001). In vivo, B7H4-overexpressing tumor cells showed enhanced tumor growth in immunocompetent mice with impaired CD8 T cell infiltration of the tumor. Further investigation showed that activation and expansion of CD8 T cells within the lymph nodes were suppressed in B7H4-overexpessing tumor-bearing mice. An in vitro killing assay showed that the cytotoxicity of CD8 T cells was inhibited in B7H4-overexpressing tumor cells. These findings suggest that B7H4 in tumor cells is a negative regulator of CD8 T cell activation, expansion and cytotoxicity, indicating that tumor cell-associated B7H4 might be a target for T cell-based cancer immunotherapy.

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Title: B7H4 expression in tumor cells impairs CD8 T cell responses and tumor immunity
Authors: Linlin Zhou
Mei Ruan
Ying Liu
Yanyang Zhu
Deqiang Fu
Kunlin Wu
Qiuyu Zhang
Publication date: 01-02-2020
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 2/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02451-4

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