作者
Mayuki Omatsu, Yuki Nakanishi, Kosuke Iwane, Naoki Aoyama, Angeles Duran, Yu Muta, Anxo Martinez-Ordoñez, Qixiu Han, Nobukazu Agatsuma, Kenta Mizukoshi, Munenori Kawai, Go Yamakawa, Mio Namikawa, Kensuke Hamada, Yuichi Fukunaga, Takahiro Utsumi, Makoto Sono, Tomonori Masuda, Akitaka Hata, Osamu Araki, Munemasa Nagao, Takaaki Yoshikawa, Satoshi Ogawa, Yukiko Hiramatsu, Motoyuki Tsuda, Takahisa Maruno, Toshiaki Kogame, Hiroaki Kasashima, Nobuyuki Kakiuchi, Masahiro M Nakagawa, Kenji Kawada, Masakazu Yashiro, Kiyoshi Maeda, Yasuyuki Saito, Takashi Matozaki, Akihisa Fukuda, Kenji Kabashima, Kazutaka Obama, Seishi Ogawa, Nader Sheibani, Maria T Diaz-Meco, Jorge Moscat, Hiroshi Seno
发表日期
2023/9/25
期刊
Nature Communications
卷号
14
期号
1
页码范围
5534
出版商
Nature Publishing Group UK
简介
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 …
学术搜索中的文章
M Omatsu, Y Nakanishi, K Iwane, N Aoyama, A Duran… - Nature Communications, 2023