D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1

Significance PD-L1 is well known as an immune checkpoint molecule, which suppresses immune surveillance through binding to its receptor PD-1. Intracellular PD-L1 can also protect messenger RNAs of several DNA damage repair–related genes from degradation and enhance tumor resistance to DNA-damaging therapy. Triple-negative breast cancer (TNBC) has the worst prognosis and highest risk of distant relapse in breast cancer and shows resistance to immunotherapy and radiotherapy. In this study, we found that D-mannose can promote the degradation of PD-L1 and significantly enhance immunotherapy and radiotherapy of TNBC. Since TNBC treatment is still a clinical challenge, our findings provide strategies to enhance the therapeutic efficacy of TNBC and may have clinical application.