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

Jing, Zhi-liang1,2,3,4; Liu, Guang-long1,2,3; Zhou, Na5; Xu, Dong-yan1,2,3; Feng, Na6; Lei, Yan1,2,3; Ma, Li-li7; Tang, Min-shan1,2,3; Tong, Gui-hui8; Tang, Na9; Deng, Yong-jian1,2,3

2024-03-13

10.1038/s41598-024-56681-3

SCIENTIFIC REPORTS   影响因子和分区

2045-2322

The bioactivity of interferon-gamma (IFN-gamma) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-gamma 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-gamma 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-gamma 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-gamma/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Colorectal cancer Tumor microenvironment IFN-gamma CD8(+) T cells Immune cytotoxicity

SCI

英语

通讯

National Natural Science Foundation of China["81672453","81702359"] ; Science and Technology Foundation of Shenzhen["JCYJ20210324114402006","JCYJ20180301170035531"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001185520800025

NATURE PORTFOLIO

Web of Science

1.Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou 510515, Peoples R China
2.Southern Med Univ, Nan Fang Hosp, Guangzhou 510515, Peoples R China
3.Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Peoples R China
4.Guangdong Med Univ, Affiliated Hosp, Dept Pathol, Zhanjiang 524001, Peoples R China
5.Guangdong Prov Hosp Tradit Chinese Med, Dept Pathol, Guangzhou 510120, Peoples R China
6.Dongguan Songshan Lake Tungwah Hosp, Dept Gynaecol, Dongguan, Peoples R China
7.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Pathol, Guangzhou, Peoples R China
8.Guangzhou Med Univ, Affiliated Hosp 1, Dept Pathol, Guangzhou 510415, Peoples R China
9.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Dept Pathol,Shenzhen Peoples Hosp,Clin Med Coll 2, Shenzhen 518020, Peoples R China

Jing, Zhi-liang,Liu, Guang-long,Zhou, Na,et al. Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells[J]. SCIENTIFIC REPORTS,2024,14(1).

Jing, Zhi-liang.,Liu, Guang-long.,Zhou, Na.,Xu, Dong-yan.,Feng, Na.,...&Deng, Yong-jian.(2024).Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.SCIENTIFIC REPORTS,14(1).

Jing, Zhi-liang,et al."Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells".SCIENTIFIC REPORTS 14.1(2024).