Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer

Shakiba, Mojdeh, Tuveson, David A (April 2025) Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer. Nature Immunology. ISSN 1529-2908

URL: https://www.ncbi.nlm.nih.gov/pubmed/40263612

DOI: 10.1038/s41590-025-02134-6

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers that has yet to benefit from immunotherapies. This is primarily a result of its characteristic 'cold' tumor microenvironment composed of cancer-associated fibroblasts (CAFs), a dense network of extracellular matrix and several immune cell types, the most abundant of which are the tumor-associated macrophages (TAMs). Advances in single-cell and spatial technologies have elucidated the vast functional heterogeneity of CAFs and TAMs, their symbiotic relationship and their cooperative role in the tumor microenvironment. In this Review, we provide an overview of the heterogeneity of CAFs and TAMs, how they establish an immunosuppressive microenvironment and their collaboration in the remodeling of the extracellular matrix. Finally, we examine why the impact of immunotherapy in PDAC has been limited and how a detailed molecular and spatial understanding of the combined role of CAFs and TAMs is paramount to the design of effective therapies.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages organs, tissues, organelles, cell types and functions > cell types and functions > cell types > macrophages organs, tissues, organelles, cell types and functions diseases & disorders > cancer > cancer types > pancreatic cancer diseases & disorders > cancer > cancer types
CSHL Authors:	Tuveson, David A. Shakiba, Mojdeh
Communities:	CSHL labs > Tuveson lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	22 April 2025
Date Deposited:	23 Apr 2025 13:35
Last Modified:	23 Apr 2025 13:35
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41856

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