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

TL;DR

Combining β-glucan with PD-L1 blockade improves ablation therapy outcomes in pancreatic cancer by boosting anti-tumor immunity.

Contribution

First proposal of combining DC-trained immunity with MWA therapy for pancreatic cancer.

Findings

β-glucan increased MHCII+DCs and improved anti-tumor immunity in mice.

Combination therapy suppressed residual tumor growth and prolonged survival.

β-glucan reversed immunosuppressive TME after ablation.

Abstract

•First proposal of “DC-trained immunity combined MWA therapy” for pancreatic cancer.•Trained DCs reshape post-ablation immunosuppressive tumor microenvironment.•High clinical potential with broad applicability to improve ablation outcomes.

First proposal of “DC-trained immunity combined MWA therapy” for pancreatic cancer.

Trained DCs reshape post-ablation immunosuppressive tumor microenvironment.

High clinical potential with broad applicability to improve ablation outcomes.

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

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.

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.

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.

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