Details

Autor(en) / Beteiligte

• Omatsu, Mayuki
• Nakanishi, Yuki
• Iwane, Kosuke
• Aoyama, Naoki
• Duran, Angeles
• Muta, Yu
• Martinez-Ordoñez, Anxo
• Han, Qixiu
• Agatsuma, Nobukazu
• Mizukoshi, Kenta
• Kawai, Munenori
• Yamakawa, Go
• Namikawa, Mio
• Hamada, Kensuke
• Fukunaga, Yuichi
• Utsumi, Takahiro
• Sono, Makoto
• Masuda, Tomonori
• Hata, Akitaka
• 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
• Maeda, Kiyoshi
• Saito, Yasuyuki
• Matozaki, Takashi
• Fukuda, Akihisa
• Kabashima, Kenji
• Obama, Kazutaka
• Ogawa, Seishi
• Sheibani, Nader
• Diaz-Meco, Maria T
• Moscat, Jorge
• Seno, Hiroshi

Titel

THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer

Ist Teil von

• Nature communications, 2023-09, Vol.14 (1), p.5534-5534, Article 5534

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.