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Tumor-secreted IFI35 promotes proliferation and cytotoxic activity of CD8+ T cells through PI3K/AKT/mTOR signaling pathway in colorectal cancer.
Li, Peisi; Zhou, Dawang; Chen, Dongwen; Cheng, Yikan; Chen, Yuan; Lin, Zhensen; Zhang, Xi; Huang, Zhihong; Cai, Jiawei; Huang, Wenfeng; Lin, Yanyun; Ke, Haoxian; Long, Jiahui; Zou, Yifeng; Ye, Shubiao; Lan, Ping.
Afiliación
  • Li P; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Zhou D; School of Medicine, Sun Yat-Sen University, Shenzhen, Guangdong, People's Republic of China.
  • Chen D; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
  • Cheng Y; Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou, People's Republic of China.
  • Chen Y; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Lin Z; Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Zhang X; School of Medicine, Sun Yat-Sen University, Shenzhen, Guangdong, People's Republic of China.
  • Huang Z; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Cai J; Guangzhou Biosyngen Co., Ltd., Guangdong, People's Republic of China.
  • Huang W; Guangzhou Biosyngen Co., Ltd., Guangdong, People's Republic of China.
  • Lin Y; Department of General Surgery (Department of Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangdong, Guangzhou, People's Republic of China.
  • Ke H; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Long J; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Zou Y; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Ye S; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
  • Lan P; Guangdong Institute of Gastroenterology; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China. zouyif@mail.sysu.edu.cn.
J Biomed Sci ; 30(1): 47, 2023 Jun 28.
Article en En | MEDLINE | ID: mdl-37380972
BACKGROUND: A large proportion of the patients with cancer do not respond to immunotherapies. Recent studies suggested an important role for tumor-infiltrating cytotoxic T lymphocytes (CTL) in enhancing response to immunotherapy. Here, we aim to identify gene that induce proliferative and cytotoxic states of CD8+ T cells, and to investigate its effect on CAR-T cells against colorectal cancer. METHODS: Correlation between the expression of IFI35 with the activation and cytotoxicity of CD8+ T cells was assessed with TCGA and proteomic databases. Then we constructed murine colon cancer cells over-expressing IFI35 and tested their effect on anti-tumor immunity in both immunodeficient and immunocompetent mouse models. Flow cytometry and immunohistochemistry were performed to assess the immune microenvironment. Western blot analysis was used to identify the potential down-stream signaling pathway regulated by IFI35. We further investigated the efficacy of the rhIFI35 protein in combination with immunotherapeutic treatment. RESULTS: The transcriptional and proteomic analysis of the activation and cytotoxicity of CD8+ T cells in human cancer samples demonstrated that IFI35 expression is correlated with increased CD8+ T cell infiltration and predicted a better outcome in colorectal cancer. The number and cytotoxicity of CD8+ T cells were significantly increased in IFI35-overexpressing tumors. Mechanistically, we identified that the IFNγ-STAT1-IRF7 axis stimulated IFI35 expression, and that IFI35-mediated regulation of CD8+ T cell proliferation and cytotoxicity was dependent on PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, IFI35 protein enhanced the efficacy of CAR-T cells against colorectal cancer cells. CONCLUSION: Our findings identify IFI35 as a new biomarker that can enhance the proliferation and function of CD8+ T cells, as well as increase the efficacy of CAR-T cells against colorectal cancer cells.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias del Colon / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Biomed Sci Asunto de la revista: MEDICINA Año: 2023 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias del Colon / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Biomed Sci Asunto de la revista: MEDICINA Año: 2023 Tipo del documento: Article