Huaier Polysaccharides Sensitize Anti-PD-L1 Therapy via Promoting Antitumor Immune Response in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and resistance to conventional therapies. Although immune checkpoint inhibitors (ICIs) have shown promise in cancer treatment, TNBC patients respond suboptimally to ICIs as monotherapy. Our prior clinical research demonstrated that Huaier significantly improved 5-year overall survival and disease-free survival when used as an adjunct to chemotherapy in TNBC patients. However, whether PS-T (the primary component of Huaier granules) enhances the efficacy of ICIs against TNBC and the underlying mechanisms remain unclear. In this study, we found that combining anti-PD-L1 antibodies with PS-T synergistically suppressed tumor growth and cell proliferation in TNBC, accompanied by enhanced antitumor immune responses. Mechanistically, PS-T promoted the autophagic degradation of PD-L1, which in turn facilitated the accumulation and activation of CD45+, CD3+ T, CD4+ T, CD8+ T, and dendritic cells, while reducing immunosuppressive regulatory T cells, ultimately enhancing the efficacy of anti-PD-L1 antibodies.