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Interferon‑γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells

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机构： [1]Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China [3]Department of Pathology, Afliated Hospital of Guangdong Medical University, Zhanjiang 524001, China [4]Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China [5]Department of Pathology, Dongguan Songshan Lake Tungwah Hospital, Dongguan 523413, China [6]Department of Pathology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China [7]Department of Pathology, The First Afliated Hospital of Guangzhou Medical University, Guangzhou 510415, China [8]Department of Pathology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Afliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China

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The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.© 2024. The Author(s).

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出版当年[2023]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

最新[2025]版：

大类 | 3 区综合性期刊

小类 | 3 区综合性期刊

第一作者：

第一作者机构： [1]Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China [3]Department of Pathology, Afliated Hospital of Guangdong Medical University, Zhanjiang 524001, China

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通讯作者：

通讯机构： [1]Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China [2]Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou 510515, China

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