Date
2020Journal
JCI insightPublisher
The American Society for Clinical InvestigationType
Article
Metadata
Show full item recordAbstract
Immune checkpoint blockade immunotherapy delivers promising clinical results in colorectal cancer (CRC). However, only a fraction of cancer patients develop durable responses. The tumor microenvironment (TME) negatively impacts tumor immunity and subsequently clinical outcomes. Therefore, there is a need to identify other checkpoint targets associated with the TME. Early-onset factors secreted by stromal cells as well as tumor cells often help recruit immune cells to the TME, among which are alarmins such as IL-33. The only known receptor for IL-33 is stimulation 2 (ST2). Here we demonstrated that high ST2 expression is associated with poor survival and is correlated with low CD8+ T cell cytotoxicity in CRC patients. ST2 is particularly expressed in tumor-associated macrophages (TAMs). In preclinical models of CRC, we demonstrated that ST2-expressing TAMs (ST2+ TAMs) were recruited into the tumor via CXCR3 expression and exacerbated the immunosuppressive TME; and that combination of ST2 depletion using ST2-KO mice with anti-programmed death 1 treatment resulted in profound growth inhibition of CRC. Finally, using the IL-33trap fusion protein, we suppressed CRC tumor growth and decreased tumor-infiltrating ST2+ TAMs. Together, our findings suggest that ST2 could serve as a potential checkpoint target for CRC immunotherapy.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084382676&doi=10.1172%2fjci.insight.136073&partnerID=40&md5=8bcd537fb1e05f8ca72c0a9350fe8caa; http://hdl.handle.net/10713/12818ae974a485f413a2113503eed53cd6c53
10.1172/jci.insight.136073
Scopus Count
Collections
Related articles
- Tumor-Infiltrating Regulatory T-cell Accumulation in the Tumor Microenvironment Is Mediated by IL33/ST2 Signaling.
- Authors: Son J, Cho JW, Park HJ, Moon J, Park S, Lee H, Lee J, Kim G, Park SM, Lira SA, Mckenzie AN, Kim HY, Choi CY, Lim YT, Park SY, Kim HR, Park SH, Shin EC, Lee I, Ha SJ
- Issue date: 2020 Nov
- The IL-33/ST2 pathway shapes the regulatory T cell phenotype to promote intestinal cancer.
- Authors: Pastille E, Wasmer MH, Adamczyk A, Vu VP, Mager LF, Phuong NNT, Palmieri V, Simillion C, Hansen W, Kasper S, Schuler M, Muggli B, McCoy KD, Buer J, Zlobec I, Westendorf AM, Krebs P
- Issue date: 2019 Jul
- IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE<sub>2</sub>.
- Authors: Li Y, Shi J, Qi S, Zhang J, Peng D, Chen Z, Wang G, Wang Z, Wang L
- Issue date: 2018 Aug 17
- Therapeutic potential of anti-VEGF receptor 2 therapy targeting for M2-tumor-associated macrophages in colorectal cancer.
- Authors: Min AKT, Mimura K, Nakajima S, Okayama H, Saito K, Sakamoto W, Fujita S, Endo H, Saito M, Saze Z, Momma T, Ohki S, Kono K
- Issue date: 2021 Feb
- IL-33/ST2 pathway contributes to metastasis of human colorectal cancer.
- Authors: Liu X, Zhu L, Lu X, Bian H, Wu X, Yang W, Qin Q
- Issue date: 2014 Oct 24