1. Academic Validation
  2. Myeloid-derived suppressor cells cross-talk with B10 cells by BAFF/BAFF-R pathway to promote immunosuppression in cervical cancer

Myeloid-derived suppressor cells cross-talk with B10 cells by BAFF/BAFF-R pathway to promote immunosuppression in cervical cancer

  • Cancer Immunol Immunother. 2022 Jun 20. doi: 10.1007/s00262-022-03226-0.
Ding Jianyi  # 1 Gan Haili  # 1 Yin Bo  # 1 Yang Meiqin 1 Huang Baoyou 1 Hu Haoran 1 Li Fang 2 Zheng Qingliang 3 Han Lingfei 4
Affiliations

Affiliations

  • 1 Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201240, China.
  • 2 Department of Gynecology, School of Medicine, Shanghai East Hospital, Tongji University, Shanghai, 200120, China. lifang@126.Com.
  • 3 Sun Yat-sen University, Prenatal Diagnosis Center, The Eighth Affiliated Hospital, Shenzhen, 518000, People's Republic of China. Zhengql82@126.com.
  • 4 Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201240, China. lingfeihan@126.com.
  • # Contributed equally.
Abstract

Immunosuppression induced by myeloid-derived suppressor cells (MDSCs) is one of the main obstacles to the efficacy of immunotherapy for cervical Cancer. Recent studies on the immunosuppressive ability of MDSCs have primarily focused on T cells, but the effect of MDSCs on B cells function is still unclear. In a study of clinical specimens, we found that the accumulation of MDSCs in patients with cervical Cancer was accompanied by high expression of B cell activating factor (BAFF) on the surface and high expression of interleukin (IL)-10-producing B cells (B10) in vivo. We found that the absence of BAFF could significantly inhibit tumor growth in a cervical Cancer model using BAFF KO mice. Further studies showed that abundant MDSCs in cervical Cancer induced B cells to differentiate into B10 cells by regulating BAFF which acted on the BAFF Receptor (BAFF-R) of them. In this process, we found that a large amount of IL-10 secreted by B10 cells can activate STAT3 signaling pathway in MDSCs, and then form a positive feedback loop to promote the differentiation of B10 cells. Therefore, this study reveals a new mechanism of BAFF-mediated mutual immune regulation between MDSCs and B cells in the occurrence and development of cervical Cancer.

Keywords

BAFF; Cervical cancer; Interleukin (IL)-10-producing B cells (B10); Myeloid-derived suppressor cells (MDSCs); STAT3.

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