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

Cancer Immunol Immunother. 2023 Jan;72(1):73-85. doi: 10.1007/s00262-022-03226-0. Epub 2022 Jun 20.

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.

MeSH terms

  • Animals
  • B-Cell Activation Factor Receptor
  • Female
  • Humans
  • Immunosuppression Therapy
  • Immunotherapy
  • Mice
  • Myeloid-Derived Suppressor Cells*
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • B-Cell Activation Factor Receptor