| First Author | Wu L | Year | 2022 |
| Journal | Theranostics | Volume | 12 |
| Issue | 2 | Pages | 842-858 |
| PubMed ID | 34976216 | Mgi Jnum | J:346639 |
| Mgi Id | MGI:6854153 | Doi | 10.7150/thno.66575 |
| Citation | Wu L, et al. (2022) FcgammaRIIB potentiates differentiation of myeloid-derived suppressor cells to mediate tumor immunoescape. Theranostics 12(2):842-858 |
| abstractText | Background: FcgammaRIIB, the sole inhibitory receptor of the Fc gamma receptor family, plays pivotal roles in innate and adaptive immune responses. However, the expression and function of FcgammaRIIB in myeloid-derived suppressor cells (MDSCs) remains unknown. This study aimed to investigate whether and how FcgammaRIIB regulates the immunosuppressive activity of MDSCs during cancer development. Methods: The MC38 and B16-F10 tumor-bearing mouse models were established to investigate the role of FcgammaRIIB during tumor progression. FcgammaRIIB-deficient mice, adoptive cell transfer, mRNA-sequencing and flow cytometry analysis were used to assess the role of FcgammaRIIB on immunosuppressive activity and differentiation of MDSCs. Results: Here we show that FcgammaRIIB was upregulated in tumor-infiltrated MDSCs. FcgammaRIIB-deficient mice showed decreased accumulation of MDSCs in the tumor microenvironment (TME) compared with wild-type mice. FcgammaRIIB was required for the differentiation and immunosuppressive activity of MDSCs. Mechanistically, tumor cell-derived granulocyte-macrophage colony stimulating factor (GM-CSF) increased the expression of FcgammaRIIB on hematopoietic progenitor cells (HPCs) by activating specificity protein 1 (Sp1), subsequently FcgammaRIIB promoted the generation of MDSCs from HPCs via Stat3 signaling. Furthermore, blockade of Sp1 dampened MDSC differentiation and infiltration in the TME and enhanced the anti-tumor therapeutic efficacy of gemcitabine. Conclusion: These results uncover an unrecognized regulatory role of the FcgammaRIIB in abnormal differentiation of MDSCs during cancer development and suggest a potential therapeutic target for anti-tumor therapy. |
