Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer
Autor: | Yanjun Qiao, Ming-Ming Feng, Lin-Lin Guo, Liqun Ye, Xiao-Hong Zhang, Hongmin Wang, Feifei Fan, Jing Chen |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
CD4-Positive T-Lymphocytes
Male Lung Neoplasms Physiology Regulatory T cell medicine.medical_treatment T cells CD8-Positive T-Lymphocytes lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Immune system Non-small cell lung cancer Carcinoma Non-Small-Cell Lung medicine Cytotoxic T cell Humans lcsh:QD415-436 Aged Interleukin-35 lcsh:QP1-981 business.industry Interleukins Interleukin Immunoregulation Cell cycle Middle Aged Neoplasm Proteins respiratory tract diseases Gene Expression Regulation Neoplastic medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis Interleukin 35 Cancer research Female business Antitumor activity CD8 030215 immunology |
Zdroj: | Cellular Physiology and Biochemistry, Vol 47, Iss 6, Pp 2407-2419 (2018) |
ISSN: | 1421-9778 1015-8987 |
Popis: | Background/Aims: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. Methods: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. Results: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. Conclusion: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC. |
Databáze: | OpenAIRE |
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