{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:18:23Z","timestamp":1787897903991,"version":"build-2784847793"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Although the role of cancer-associated fibroblasts (CAFs) in cancer progression is increasingly recognized, their spatial dynamics and interactions with immune cells remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we present a computational framework that integrates single-cell resolution spatial transcriptomics and standard spatial transcriptomics across multiple tumor types to investigate CAF heterogeneity and its roles\n                      <jats:italic>in situ<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis presents a continuous transition from fibroblast progenitors to COL11A1-expressing CAFs, which we term aggressive CAFs (aCAFs), within a spatial context. We show that aCAFs, whose expression has been associated with poor prognosis, tend to localize at tumor boundaries, where proximity to tumor cells predicts increased expression of aCAF-associated genes. Spatial modeling shows that regions enriched for COL11A1-expressing CAFs were depleted of non-exhausted immune cells, including naive T cells, activated cytotoxic T cells, and activated B cells, suggesting a role in immune exclusion. Spatial correlation analysis further reveals that aCAFs co-localize with lipid-associated macrophages, a pattern linked to extracellular matrix remodeling and altered lipid metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides insights into the interactions of aCAF, tumor cells, and immune cells in the tumor microenvironment. We also provide an open-source implementation of SpatialAttractor, a toolkit for exploring gene co-expression in the spatial context.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1886779","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:35:41Z","timestamp":1787895341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial dynamics of cancer-associated fibroblasts links fibroblastic differentiation to immune exclusion and tumor progression"],"prefix":"10.3389","volume":"17","author":[{"given":"Lingyi","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Systems Biology, Columbia University","place":["NY, United States"]},{"name":"Department of Electrical Engineering, Columbia University","place":["NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Hsien","family":"Ou Yang","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University","place":["NY, United States"]},{"name":"Department of Electrical Engineering, Columbia University","place":["NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Anastassiou","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University","place":["NY, United States"]},{"name":"Department of Electrical Engineering, Columbia University","place":["NY, United States"]},{"name":"Herbert Irving Comprehensive Cancer Center, Columbia University","place":["NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0644","article-title":"Single-cell RNA sequencing reveals stromal evolution into LRRC15+ myofibroblasts as a determinant of 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