ArticleNature communications2025
Targeting fibroblast derived thrombospondin 2 disrupts an immune-exclusionary environment at the tumor front in colorectal cancer.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10citing papers in PubMed
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Who cites it
10 citing papers in PubMed.
- Colorectal Cancer: Epidemiology, Risk Factors, Signaling Pathways, Clinical Features, Screening, Diagnosis, and Management.MedComm · 2026Review
- An integrated spatially defined roadmap of normal and cancer-associated colon fibroblasts.Molecular systems biology · 2026Article
- Review
- Formation of tertiary lymphoid structures drives Parkin antitumor immunity.Science advances · 2026Article
- Myofibroblastic CAF and Malignant Ductal Cell Crosstalk Drives Epithelial-Mesenchymal Transition and Progression in Pancreatic Ductal Adenocarcinoma via THBS2-SDC/Integrin Axes.International journal of molecular sciences · 2026Article
- Spatial Autocorrelation Aware Resampling Improves Cell-Cell Interaction Inference in Spatial Transcriptomics Data.bioRxiv : the preprint server for biology · 2026Article
- Targeting cellular source-specific CXCL9 signaling for immunotherapy in oral squamous cell carcinoma.Frontiers in immunology · 2026Review
- Multicellular immunosuppressive networks in microsatellite-stable colorectal cancer: CD8+ T cell exclusion, dysfunction, exhaustion, and therapeutic implications.Frontiers in immunology · 2026Review
- Traditional Chinese medicine remodels the immune microenvironment of colorectal cancer: mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
38 authors.
Kosuke IwaneDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yuki NakanishiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. yuki@kuhp.kyoto-u.ac.jp.ORCID http://orcid.org/0000-0001-5493-6312
Yu MutaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. yumuta@kuhp.kyoto-u.ac.jp.ORCID http://orcid.org/0000-0001-5311-363X
Jiayu ChenDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kento YasumuraDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Mayuki OmatsuDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0003-1595-7094
Naoki AoyamaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Munehiro IkedaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yoko MasuiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Liyang CaiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Go YamakawaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kensuke HamadaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kenta MizukoshiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Munenori KawaiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kei IimoriDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Shinnosuke NakayamaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nobukazu AgatsumaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takahiro UtsumiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0001-6067-3694
Munemasa NagaoDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0003-0789-6623
Takahisa MarunoDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yukiko HiramatsuDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0001-5903-8677
Nobuyuki KakiuchiDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0003-4893-5414
Masahiro M NakagawaDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.ORCID http://orcid.org/0000-0002-6420-2555
Yasuhiro FukuiDepartment of Gastroenterological Surgery, Osaka Metropolitan University Graduate Scholl of Medicine, Osaka, Japan.ORCID http://orcid.org/0000-0001-8878-883X
Yukina KusunokiDepartment of Gastroenterological Surgery, Osaka Metropolitan University Graduate Scholl of Medicine, Osaka, Japan.ORCID http://orcid.org/0009-0002-4257-729X
Hiroaki KasashimaDepartment of Gastroenterological Surgery, Osaka Metropolitan University Graduate Scholl of Medicine, Osaka, Japan.ORCID http://orcid.org/0000-0001-5234-4030
Masakazu FujimotoDepartment of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
Yoshiro ItataniDepartment of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0001-7356-7065
Toshiaki KogameDepartment of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Akihisa FukudaDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0009-0005-2215-681X
Masakazu YashiroDepartment of Gastroenterological Surgery, Osaka Metropolitan University Graduate Scholl of Medicine, Osaka, Japan.
Kiyoshi MaedaDepartment of Gastroenterological Surgery, Osaka Metropolitan University Graduate Scholl of Medicine, Osaka, Japan.
Kenji KabashimaDepartment of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID http://orcid.org/0000-0002-0773-0554
Kazutaka ObamaDepartment of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.
Maria T Diaz-MecoDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, USA.ORCID http://orcid.org/0000-0003-0147-0998
Jorge MoscatDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, USA.ORCID http://orcid.org/0000-0002-9442-3834
Hiroshi SenoDepartment of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Funding
Cabinet Office, Government of Japan JP22zf0127009Japan Agency for Medical Research and Development (AMED) 25ama221326h0001Japan Agency for Medical Research and Development (AMED) 25ama221444h0001MEXT | Japan Society for the Promotion of Science (JSPS) 23H02891MEXT | Japan Society for the Promotion of Science (JSPS) 23K27582MEXT | Japan Society for the Promotion of Science (JSPS) 25K02638
Abstract
Fibrotic colorectal cancers (CRC) are largely microsatellite-stable and display desmoplastic stroma with poor immune infiltration. Here we identify thrombospondin-2 (THBS2) as a key regulator of the immune-exclusionary phenotype in fibrotic CRC. THBS2 is highly expressed by matrix cancer-associated fibroblasts at the tumor front. In an orthotopic model using desmoplastic tumor organoids, global or fibroblast-specific Thbs2 deletion disrupts the exclusionary barrier and increases intratumoral CD8 T cells. Mechanistically, THBS2 limits recruitment of CXCR3
Indexed as
Cancer-Associated FibroblastsColorectal NeoplasmsThrombospondinsAnimalsCD8-Positive T-LymphocytesCell Line, TumorChemokine CXCL9FemaleFibroblastsFibrosisHumansMiceMice, Inbred C57BLMice, KnockoutMyeloid CellsReceptors, CXCR3Chemokine CXCL9Receptors, CXCR3Thrombospondin 2Thrombospondins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.