Loss of fragile site-associated tumor suppressor promotes antitumor immunity via macrophage polarization

Lijuan Zhang, Kai Zhang, Jieyou Zhang, Jinrong Zhu, Qing Xi, Huafeng Wang, Zimu Zhang, Yingnan Cheng, Guangze Yang, Hongkun Liu, Xiangdong Guo, Dongmei Zhou, Zhenyi Xue, Yan Li, Qi Zhang, Yurong Da, Li Liu, Zhinan Yin, Zhi Yao and Rongxin Zhang ()
Additional contact information
Lijuan Zhang: Tianjin Medical University
Kai Zhang: Tianjin Medical University
Jieyou Zhang: Tianjin Medical University
Jinrong Zhu: Guangdong Pharmaceutical University
Qing Xi: Tianjin Medical University
Huafeng Wang: Shanxi Normal University
Zimu Zhang: Tianjin Medical University
Yingnan Cheng: Tianjin Medical University
Guangze Yang: Tianjin Medical University
Hongkun Liu: Tianjin Medical University
Xiangdong Guo: Tianjin Medical University
Dongmei Zhou: Tianjin Medical University
Zhenyi Xue: Tianjin Medical University
Yan Li: Tianjin Medical University
Qi Zhang: Nankai Hospital
Yurong Da: Tianjin Medical University
Li Liu: The University of Texas Southwestern Medical Center
Zhinan Yin: Jinan University
Zhi Yao: Tianjin Medical University
Rongxin Zhang: Guangdong Pharmaceutical University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Common fragile sites (CFSs) are specific breakage-prone genomic regions and are present frequently in cancer cells. The (E2-independent) E3 ubiquitin-conjugating enzyme FATS (fragile site-associated tumor suppressor) has antitumor activity in cancer cells, but the function of FATS in immune cells is unknown. Here, we report a function of FATS in tumor development via regulation of tumor immunity. Fats−/− mice show reduced subcutaneous B16 melanoma and H7 pancreatic tumor growth compared with WT controls. The reduced tumor growth in Fats−/− mice is macrophage dependent and is associated with a phenotypic shift of macrophages within the tumor from tumor-promoting M2-like to antitumor M1-like macrophages. In addition, FATS deficiency promotes M1 polarization by stimulating and prolonging NF-κB activation by disrupting NF-κB/IκBα negative feedback loops and indirectly enhances both CD4+ T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) adaptive immune responses to promote tumor regression. Notably, transfer of Fats−/− macrophages protects mice against B16 melanoma. Together, these data suggest that FATS functions as an immune regulator and is a potential target in cancer immunotherapy.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24610-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24610-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24610-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().