Irreversible Electroporation Reverses Resistance to Immune Checkpoint Blockade in Pancreatic Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Feb 24

PMID 30796212

Citations 124

Authors

Jun Zhao

Xiaofei Wen

Li Tian

Tingting Li

Chunyu Xu

Xiaoxia Wen

Marites P Melancon

Sanjay Gupta

Baozhong Shen

Weiyi Peng

Chun Li

Affiliations

Soon will be listed here.

Abstract

Immunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) due to the presence of an immunosuppressive tumor-associated stroma. Here, we demonstrate an effective modulation of that stroma by irreversible electroporation (IRE), a local ablation technique that has received regulatory approval in the United States. IRE induces immunogenic cell death, activates dendritic cells, and alleviates stroma-induced immunosuppression without depleting tumor-restraining collagen. The combination of IRE and anti-programmed cell death protein 1 (anti-PD1) immune checkpoint blockade promotes selective tumor infiltration by CD8 T cells and significantly prolongs survival in a murine orthotopic PDAC model with a long-term memory immune response. Our results suggest that IRE is a promising approach to potentiate the efficacy of immune checkpoint blockade in PDAC.

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