Targeting myeloid derived suppressor cells reverts immune suppression and sensitizes BRAF-mutant papillary thyroid cancer to MAPK inhibitors

Peitao Zhang, Haixia Guan, Shukai Yuan, Huili Cheng, Jian Zheng, Zhenlei Zhang, Yifan Liu, Yang Yu, Zhaowei Meng, Xiangqian Zheng and Li Zhao ()
Additional contact information
Peitao Zhang: Tianjin Medical University
Haixia Guan: Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences
Shukai Yuan: Tianjin Medical University
Huili Cheng: Tianjin Medical University
Jian Zheng: Tianjin Medical University
Zhenlei Zhang: Tianjin Medical University
Yifan Liu: Tianjin Medical University
Yang Yu: Tianjin Medical University Cancer Institute and Hospital
Zhaowei Meng: Tianjin Medical University General Hospital
Xiangqian Zheng: Tianjin Medical University Cancer Institute and Hospital
Li Zhao: Tianjin Medical University

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract MAPK signaling inhibitor (MAPKi) therapies show limited efficacy for advanced thyroid cancers despite constitutive activation of the signaling correlates with disease recurrence and persistence. Understanding how BRAF pathway stimulates tumorigenesis could lead to new therapeutic targets. Here, through genetic and pathological approaches, we demonstrate that BRAFV600E promotes thyroid cancer development by increasing myeloid-derived suppressor cells (MDSCs) penetrance. This BRAFV600E-induced immune suppression involves re-activation of the developmental factor TBX3, which in turn up-regulates CXCR2 ligands in a TLR2-NFκB dependent manner, leading to MDSCs recruitment into the tumor microenvironment. CXCR2 inhibition or MDSCs repression improves MAPKi therapy effect. Clinically, high TBX3 expression correlates with BRAFV600E mutation and increased CXCR2 ligands, along with abundant MDSCs infiltration. Thus, our study uncovers a BRAFV600E-TBX3-CXCLs-MDSCs axis that guides patient stratification and could be targeted to improve the efficacy of MAPKi therapy in advanced thyroid cancer patients.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29000-5 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:13:y:2022:i:1:d:10.1038_s41467-022-29000-5

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

DOI: 10.1038/s41467-022-29000-5

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 ().