Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics

Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics

BackgroundProstate cancer (PCa) presents substantial heterogeneity and unpredictability in its progression. Despite therapeutic advancements, mortality from advanced PCa remains a significant challenge. Understanding the intercellular communication within the tumor microenvironment (TME) is critical...

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Bibliographic Details
Main Authors: Tingting Wu, Xinyu Li, Fei Zheng, Hanchao Liu, Yang Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
Subjects:
prostate cancer
tumor microenvironment
cellular crosstalk
single-cell RNA sequencing
spatial transcriptomics
FAP+ fibroblasts
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560998/full
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Summary:BackgroundProstate cancer (PCa) presents substantial heterogeneity and unpredictability in its progression. Despite therapeutic advancements, mortality from advanced PCa remains a significant challenge. Understanding the intercellular communication within the tumor microenvironment (TME) is critical for uncovering mechanisms driving tumorigenesis and identifying novel therapeutic targets.MethodsWe employed an integrative approach combining bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to investigate interactions between FAP+ fibroblasts and tumor-associated macrophages in PCa. Key findings were validated using immunohistochemical and immunofluorescence staining techniques.ResultsAnalysis of 23,519 scRNA-seq data from 23 prostate samples revealed a pronounced accumulation of FAP+ fibroblasts in tumor tissues. Spatial transcriptomics and bulk RNA sequencing demonstrated strong associations between FAP+ fibroblasts and SPP1+ macrophages. Notably, tumor-specific intercellular signaling pathways, such as CSF1/CSF1R and CXCL/ACKR1, were identified, highlighting their potential role in fostering an immunosuppressive TME.ConclusionOur findings unveil a distinct pattern of crosstalk between FAP+ fibroblasts and SPP1+ macrophages in PCa, shedding light on potential therapeutic targets for advanced PCa.
ISSN:1664-3224

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