β-glucan combined with PD-1/PD-L1 checkpoint blockade suppresses pancreatic tumor growth after ablation therapy.

BACKGROUND

To explore whether β-glucan combined with anti-PD-L1 reverses the immunosuppressive Tumor Microenvironment (TME) in residual pancreatic cancer after Microwave Ablation (MWA).

METHODS

The effect of β-glucan on the activation of Dendritic Cells (DCs) was assessed in vitro. Subcutaneous and orthotopic pancreatic tumor models with incomplete MWA were treated with β-glucan, anti-PD-L1, or both. Tumor growth, immune cell populations in TME, and survival were analyzed.

RESULTS

β-glucan elevated MHCII+DCs, meanwhile combination therapy increased the CD8+/Treg ratio, suggesting enhanced anti-tumor immunity. This immunomodulatory effect translated into the combination therapy demonstrated significantly greater efficacy in suppressing residual tumor growth and prolonging overall survival.

CONCLUSION

β-glucan administration increased MHCII+DCs, and in combination therapy, this led to an elevated CD8+/Treg ratio, enhancing the anti-tumor immunity. β-glucan therapy reversed the immunosuppressive TME in pancreatic cancer following MWA ablation, thereby enhancing the anti-PD-L1-associated antitumor responses. This resulted in a significant suppression of residual tumor growth, leading to prolonged survival in mice establishing orthotopic pancreatic tumors.