Lentinan-laden microspheres reprogram the tumor microenvironment and improve anti-PD-L1 efficacy

Abstract

Immunotherapies are a promising new class of anticancer treatments, but the immunosuppressive tumor microenvironment (TME) hinders their broader implementation. Here, we designed a ‘3C’ strategy based on the conventional drug lentinan (LNT), applying the convertible material polylactic acid with controlled release of LNT (LNT@Mic). Our findings revealed that LNT@Mic exhibited effective biocompatibility coupled with controlled long-term release of LNT. Due to these characteristics, LNT@Mic reprogramed the immunosuppressive TME and demonstrated substantial antitumor activity in the MC38 tumor model. Furthermore, it served as a facile and generalizable cancer immunotherapy strategy for augmenting LNT bioavailability while enhancing the efficacy of anti-programmed death-ligand 1 therapy against the ‘cold’ 4T1 tumor model. These findings provide a reference for tumor immunotherapy strategies for the further study and application of LNT.