THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer
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- Omatsu, Mayuki
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Nakanishi, Yuki
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Iwane, Kosuke
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Aoyama, Naoki
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Duran, Angeles
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine
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- Muta, Yu
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine; Present address: Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Martinez-Ordoñez, Anxo
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine
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- Han, Qixiu
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine
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- Agatsuma, Nobukazu
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Mizukoshi, Kenta
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Kawai, Munenori
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Yamakawa, Go
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Namikawa, Mio
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Hamada, Kensuke
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Fukunaga, Yuichi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine; Cancer Research Unit, Sumitomo Pharma Co., Ltd
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- Utsumi, Takahiro
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Sono, Makoto
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Masuda, Tomonori
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Hata, Akitaka
- Department of Dermatology, Kyoto University Graduate School of Medicine
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- Araki, Osamu
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Nagao, Munemasa
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Yoshikawa, Takaaki
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Ogawa, Satoshi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Hiramatsu, Yukiko
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Tsuda, Motoyuki
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Maruno, Takahisa
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Kogame, Toshiaki
- Department of Dermatology, Kyoto University Graduate School of Medicine
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- Kasashima, Hiroaki
- Department of Gastroenterological Surgery, Osaka Metropolitan University
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- Kakiuchi, Nobuyuki
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine; The Hakubi Center for Advanced Research, Kyoto University
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- Nakagawa, Masahiro M.
- Department of Pathology and Tumor Biology, Kyoto University
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- Kawada, Kenji
- Department of Gastrointestinal Surgery, Kyoto University, Graduate School of Medicine
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- Yashiro, Masakazu
- Department of Gastroenterological Surgery, Osaka Metropolitan University
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- Maeda, Kiyoshi
- Department of Gastroenterological Surgery, Osaka Metropolitan University
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- Saito, Yasuyuki
- Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine
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- Matozaki, Takashi
- Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine; Division of Biosignal Regulation, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine
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- Fukuda, Akihisa
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
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- Kabashima, Kenji
- Department of Dermatology, Kyoto University Graduate School of Medicine
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- Obama, Kazutaka
- Department of Gastrointestinal Surgery, Kyoto University, Graduate School of Medicine
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- Ogawa, Seishi
- Department of Pathology and Tumor Biology, Kyoto University
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- Sheibani, Nader
- Department of Ophthalmology and Visual Sciences, University of Wisconsin-, Madison
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- Diaz-Meco, Maria T.
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine
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- Moscat, Jorge
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine
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- Seno, Hiroshi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
Abstract
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.
Journal
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- Nature Communications
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Nature Communications 14 2023-09-25
Springer Nature
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Details 詳細情報について
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- CRID
- 1050297969507605632
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- ISSN
- 20411723
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- HANDLE
- 2433/285783
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB