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Omics · study · 2026

Suppression of the myofibroblastic cancer-associated fibroblast phenotype to enhance anti-PD-1 response

Listed in NCBI GEO

Cancer-associated fibroblasts (CAFs) are key modulators of tumor growth, the tumor immune context, and treatment response.

Description

CAFs take on diverse phenotypes with distinct functions. Myofibroblastic CAFs (myCAFs) regulate extracellular matrix remodeling, while inflammatory CAFs (iCAFs) modulate immune infiltration.

Further studies are required to validate biomarkers of CAF phenotypes and to identify means to therapeutically manipulate CAFs. Here we identify disease-specific markers of colorectal CAFs that are functionally distinct, biologically identifiable, correlate with clinically relevant markers of disease, and can be therapeutically altered in vivo. High stromal expression of myCAF markers correlated with reduced infiltration of CD8+ T lymphocytes into the epithelial compartment compared to tumors with high stromal expression of iCAF markers.

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Nilotinib treatment inhibited myogenesis regulators myocardin and myocardin-related transcription factor A, which correlated with reduced expression of myCAF markers and extracellular matrix proteins, and decreased tumor size in colorectal cancer-bearing mice when combined with anti-PD-1 therapy. These results highlight the feasibility of targeting CAF functions to improve therapeutic response. We also identified PD-1 as a potential molecule that activates myocardin and myCAF expression, indicating a potential mechanism for increased response to the combination with anti-PD-1 therapy.

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From keywords
Life Sciences
Inferred from text
Cancer 65% · Disease 75%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31637312 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title