The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer
Open accessAbstract
Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis.
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“THBS1 from senescent fibroblasts was predicted to target macrophages, T/NK cells, and endothelial cells through CD47 and CD36, implicating THBS1 as a central mediator of immune modulation and anti-angiogenic signaling in senescent niches (Figure 6F).64,65,66”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [64]
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“THBS1 from senescent fibroblasts was predicted to target macrophages, T/NK cells, and endothelial cells through CD47 and CD36, implicating THBS1 as a central mediator of immune modulation and anti-angiogenic signaling in senescent niches (Figure 6F).64,65,66”
From Cellular senescence in human liver under normal aging and cancer (2026) · cites this paper as [64]
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Metadata
- Authors
- Omatsu, M., Nakanishi, Y., Iwane, K., Aoyama, N., Duran, A., Muta, Y., Martinez-Ordoñez, A., Han, Q., Agatsuma, N., Mizukoshi, K., Kawai, M., Yamakawa, G., Namikawa, M., Hamada, K., Fukunaga, Y., Utsumi, T., Sono, M., Masuda, T., Hata, A., Araki, O., Nagao, M., Yoshikawa, T., Ogawa, S., Hiramatsu, Y., Tsuda, M., Maruno, T., Kogame, T., Kasashima, H., Kakiuchi, N., Nakagawa, M. M., Kawada, K., Yashiro, M., Maeda, K., Saito, Y., Matozaki, T., Fukuda, A., Kabashima, K., Obama, K., Ogawa, S., Sheibani, N., Diaz-Meco, M. T., Moscat, J., & Seno, H.
- Affiliations
- Kyoto University (JP)
- Weill Cornell Medicine (US)
- Osaka Metropolitan University (JP)
- Kobe University (JP)
- University of Wisconsin–Madison (US)
- Corresponding author
- Nakanishi, Yuki
- ORCID
- Omatsu, Mayuki
- Nakanishi, Yuki
- Aoyama, Naoki
- Muta, Yu
- Agatsuma, Nobukazu
- Mizukoshi, Kenta
- Kawai, Munenori
- Namikawa, Mio
- Fukunaga, Yuichi
- Utsumi, Takahiro
- Sono, Makoto
- Masuda, Tomonori
- Araki, Osamu
- Nagao, Munemasa
- Yoshikawa, Takaaki
- Ogawa, Satoshi
- Hiramatsu, Yukiko
- Tsuda, Motoyuki
- Maruno, Takahisa
- Kogame, Toshiaki
- Kasashima, Hiroaki
- Kakiuchi, Nobuyuki
- Nakagawa, Masahiro M.
- Kawada, Kenji
- Yashiro, Masakazu
- Saito, Yasuyuki
- Matozaki, Takashi
- Fukuda, Akihisa
- Kabashima, Kenji
- Obama, Kazutaka
- Ogawa, Seishi
- Sheibani, Nader
- Diaz-Meco, Maria T.
- Moscat, Jorge
- Seno, Hiroshi
- Venue
- Nature Communications
- Published
- 2023-09-25
- Volume
- 14
- Issue
- 1
- Pages
- 5534-5534
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10520015
- OpenAlex
- W4387019644
- Cited by
- 109
- References
- 56
- Citations by year
- 2026: 40 · 2025: 41 · 2024: 25 · 2023: 3
- FWCI
- 11.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- Japan Agency for Medical Research and Development (21cm0106283h0001, 22cm0106283h0002, 20cm0106177h0001, 18cm0106142h0001, 20cm0106375h0001)
- MEXT | Japan Science and Technology Agency (FOREST, 23719768, JPMJMS2022-1)
- MEXT | Japan Society for the Promotion of Science (21H02902, 19H03639, 21K19480, 20H03659)
- MEXT | Japan Agency for Marine-Earth Science and Technology (22ama221515h0001)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- thrombospondin-1, colorectal cancer, tumor-infiltrating monocytes, immunosuppression, metastasis, CXCL12, bone marrow-derived monocytes, tumor vascularization, immune checkpoint inhibitors, prognostic factors, antitumor immunity
- MeSH terms
- Immune Checkpoint Inhibitors, Aggression, Animals, Humans, Immunosuppression Therapy, Male, Monocytes, Colorectal Neoplasms, Mice, Tumor Microenvironment
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