A ß-1,3/1,6-glucan from Durvillaea Antarctica enhances anti-tumor effects of immune checkpoint inhibitor antibodies
Immunotherapy has emerged as a frontline approach in cancer management, aiming to enhance the adaptive immune response against tumors. However, its limited efficacy across a narrow range of tumor types necessitates the exploration of novel strategies that target innate immunity. Therapeutic modulation of pattern recognition receptors (PRRs) and innate immune cells holds promise in tumor eradication. ß-glucan, a pathogen-associated molecular pattern (PAMP), acts as an immunostimulator, bridging the innate and adaptive immune responses. It exhibits low toxicity and high compatibility with various antitumor strategies. Plenty of clinical trials are ongoing to evaluate ß-glucan-based cancer immunotherapy and shows promising clinical benefits across multiple cancer types. A soluble ß-1,3/1,6-glucan with high purity from Durvillaea Antarctica (BG136) was reported previously by our group to exhibit pan antitumor effects alone as an immune stimulator. In current study, we proved the antitumor activity of BG136 in combination with anti-PD-1 antibodies in MC38 syngeneic tumor model in vivo. Integrated transcriptomic and metabolomic analyses suggest that BG136 enhances the antitumor immunity of anti-PD-1 antibodies by reprogramming tumor microenvironment to more proinflammatory status. There are more innate and adaptive immune cell infiltration and activation, enhanced lipid metabolism, decreased ascorbate and aldarate metabolism. These findings provide mechanistic insights supporting the potent antitumor efficacy of BG136 in combination with immune checkpoint inhibitor antibodies. Overall design: In order to assess the in vivo antitumor efficacy of BG136, a highly purified soluble ß-1,3/1,6-glucan extracted from Antarctic rhododendron, in combination with anti-PD-1 antibody, we developed a mouse MC38 syngeneic tumor model. Subsequently, tumor blocks from various treatment groups, comprising vector control and BG136 alone, were collected for gene expression profiling analysis.