Tumor-Infiltrating Mast Cells Confer Resistance to Immunotherapy in Pancreatic Cancer

Authors

Ying Ma
Xiangqin Zhao
Jingyan Feng
Suimin Qiu
Baoan Ji
Lu Huang
Patrick Hwu
Craig D Logsdon
Huamin Wang

Publication Date

11-15-2024

Journal

iScience

Abstract

Pancreatic ductal adenocarcinoma (PDAC) exhibits an immunosuppressive tumor microenvironment (TME) contributing to its therapeutic resistance. Following our previous studies, we report that mast cells infiltrating the PDAC TME foster this immunosuppression and desmoplasia. Mast cell infiltration correlated with human PDAC progression, and genetic or pharmacological mast cell depletion reduced tumor growth and desmoplasia while enhancing survival in mouse PDAC models. Mechanistically, mast cell-derived IL-10 promoted PDAC progression. Strikingly, combining an agonistic anti-OX40 immunotherapy with mast cell blockade synergistically elicited durable anti-tumor immunity, marked by increased infiltration of CD8

Keywords

Molecular biology, Neuroscience, Immunology, Cancer

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Associated Data

PMID: 39473974