IL-6 secretion of CD4+ T cells stimulated by LC3-positive extracellular vesicles in human epithelial ovarian cancer

• Xiu-Lin Zhu ^[1] ; Hao-Jue Wang ^[2] ; Xu-Ru Wang ^[1] ; Di Wu ^[3] ; Xuan Ji ^[1] ; Li Xu ^[1] ; Qi Yang ^[1] ; Jie-Ying Guo ^[1] ; Yan Rong ^[1] ; Ning Pan ^[1] ; Yun-lang Cai ^[3]
  1. [1] Department of Microbiology and Immunology, Medical School of Southeast University, 87 Dingjiaqiao Rd., Nanjing, 210009, Jiangsu, China
  2. [2] Department of Obstetrics and Gynecology, Xishan People’s Hospital of Wuxi City, 1128 Dacheng Rd., Wuxi, 214000, Jiangsu, China
  3. [3] Department of Obstetrics and Gynecology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao Rd., Nanjing, 210009, Jiangsu, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 11 (November), 2022, págs. 2222-2230
• Idioma: inglés
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• Resumen

  • Background Ovarian cancer (OC) as the most fatal gynecological malignancy worldwide, with epithelial ovarian cancer (EOC) being the predominant and most lethal form, poses a serious threat to human health. LC3-positive extracellular vesicles (LC3+ EVs) promote tumorigenesis by educating CD4+ T cells in a murine melanoma model. However, regulation of LC3+ EVs in human EOC remains largely unknown.

    Methods Differential analysis of Rab8a, Hsp90α and Il6 expression was performed using GEPIA2. The number of LC3+ EVs and the frequency of Heat shock protein 90α+ LC3+ EVs (HSP90α+ LC3+ EVs) in the ascites of EOC patients were tested by flow cytometry. IL-6, IL-10, IFN-γ, IL-4 and TGF-β were measured by ELISA. CD4+ T cells were isolated from peripheral blood of healthy human donors using MACS magnetic bead technology.

    Results Higher Rab8a, Hsp90a and Il6 expression of cancer tissues compared with normal adjacent tissues in OC were found. The level of IL-6 was positively correlated with LC3+ EVs number, HSP90α+ LC3+ EVs percentage in the ascites, and ROMA index of the patient. In addition, elevated IL-6 production by CD4+ T cells induced by LC3+ EVs was observed, which was suppressed by anti-HSP90α or anti-TLR2.

    Conclusions LC3+ EVs level and HSP90α+ LC3+ EVs percentage were associated with elevated IL-6 in the ascites of EOC patients. HSP90α on LC3+ EVs from human EOC could stimulate CD4+ T cell production of IL-6 via TLR2.