Targeting tumorous Circ-E-Cadherinencoded C-E-Cad inhibits the recruitment and function of breast cancer-associated myeloid-derived suppressor cells.

We previously demonstrated that the C-E-cad protein encoded by circ-E-cadherin promotes the self-renewal of glioma stem cells. The expression pattern of C-E-cad in breast cancer and its potential function in the tumor microenvironment are unclear. The expression of circ-E-cadherin and C-E-cad was detected in breast cancer specimens. The influence of C-E-cad expression on MDSCs was assessed using FACS and in vivo tumorigenesis experiments. The synergistic effect of anti-C-E-cad and anti-PD-1 antibodies was validated in vivo. circ-E-cadherin and the encoded protein C-E-cad were found to be upregulated in breast cancer vs. normal samples. C-E-cad promotes the recruitment of MDSCs, especially PMN-MDSCs. C-E-cad activates EGFR signaling in tumor cells and promotes the transcription of CXCL8; moreover, C-E-cad binds to MDSCs and maintains glycolysis in PMN-MDSCs. Targeting C-E-cad enhanced anti-PD-1 efficiency. Our data suggested that C-E-cad is markedly overexpressed in breast cancer and promotes MDSC recruitment and survival. Targeting C-E-cad increases the efficacy of immune checkpoint inhibitor therapy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests The authors declare no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)