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Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.
Jing, Zhi-Liang; Liu, Guang-Long; Zhou, Na; Xu, Dong-Yan; Feng, Na; Lei, Yan; Ma, Li-Li; Tang, Min-Shan; Tong, Gui-Hui; Tang, Na; Deng, Yong-Jian.
Afiliación
  • Jing ZL; Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • Liu GL; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515, China.
  • Zhou N; Department of Pathology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
  • Xu DY; Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • Feng N; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515, China.
  • Lei Y; Department of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, 510120, China.
  • Ma LL; Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • Tang MS; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515, China.
  • Tong GH; Department of Pathology, Dongguan Songshan Lake Tungwah Hospital, Dongguan, 523413, China.
  • Tang N; Department of Pathology, School of Basic Medical Sciences and Nan Fang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • Deng YJ; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, 510515, China.
Sci Rep ; 14(1): 6053, 2024 03 13.
Article en En | MEDLINE | ID: mdl-38480774
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Neoplasias Colorrectales Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Neoplasias Colorrectales Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido