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. 2025 Jul 24;23(7):e3003276.
doi: 10.1371/journal.pbio.3003276. eCollection 2025 Jul.

TiME for a change: The tumor microenvironment as the missing piece in cancer therapeutics

Jeremy Mo  1   2 , Hanyun Zhang  1   2 , Alexander Swarbrick  1   2
Affiliations

TiME for a change: The tumor microenvironment as the missing piece in cancer therapeutics

Jeremy Mo et al. PLoS Biol. .

Abstract

Cancer treatments often fall short of durable cures, yet most therapeutic strategies neglect the tumor stroma. A concerted effort is needed to understand, model, target and reprogram the tumor 'soil', recognizing its profound influence on cancer from tumorigenesis to therapy resistance.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: AS has received research support from 10X Genomics and Phenomic.AI. AS receives research support and consulting fees from Myeloid therapeutics.

Figures

Fig 1
Fig 1. Context-dependent crosstalk between cancer associated fibroblasts and the tumor microenvironment.
A. Lung tumor with tumor-infiltrating lymphocytes, with myofibroblast-like cancer-associated fibroblasts (myCAFs) adjacent to the tumor and inflammatory CAFs (iCAFs) at the tumor periphery. B. Pancreatic tumor with antigen-presenting CAFs (apCAFs) interacting with macrophages through direct cell–cell communication and secreted factors, promoting their polarization into a pro-inflammatory phenotype. C. Pancreatic tumor, dense with myCAFs adjacent to tumor cells, with a remodeled extracellular matrix that forms a physical barrier, impeding T cell infiltration and contributing to an immune-excluded phenotype. Created in BioRender.
See this image and copyright information in PMC

Comment in

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