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ST2 as checkpoint target for colorectal cancer immunotherapy

Kevin Van der Jeught, Yifan Sun, Yuanzhang Fang, Zhuolong Zhou, Hua Jiang, Tao Yu, Jinfeng Yang, Malgorzata M. Kamocka, Ka Man So, Yujing Li, et al.
(2020) JCI INSIGHT. 5(9).
Author
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Abstract
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.
Keywords
MICROSATELLITE INSTABILITY, CELL, IL-33, EXPRESSION, INFLAMMATION, ENHANCEMENT, IMMUNITY

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MLA
Van der Jeught, Kevin, et al. “ST2 as Checkpoint Target for Colorectal Cancer Immunotherapy.” JCI INSIGHT, vol. 5, no. 9, 2020, doi:10.1172/jci.insight.136073.
APA
Van der Jeught, K., Sun, Y., Fang, Y., Zhou, Z., Jiang, H., Yu, T., … Lu, X. (2020). ST2 as checkpoint target for colorectal cancer immunotherapy. JCI INSIGHT, 5(9). https://doi.org/10.1172/jci.insight.136073
Chicago author-date
Van der Jeught, Kevin, Yifan Sun, Yuanzhang Fang, Zhuolong Zhou, Hua Jiang, Tao Yu, Jinfeng Yang, et al. 2020. “ST2 as Checkpoint Target for Colorectal Cancer Immunotherapy.” JCI INSIGHT 5 (9). https://doi.org/10.1172/jci.insight.136073.
Chicago author-date (all authors)
Van der Jeught, Kevin, Yifan Sun, Yuanzhang Fang, Zhuolong Zhou, Hua Jiang, Tao Yu, Jinfeng Yang, Malgorzata M. Kamocka, Ka Man So, Yujing Li, Haniyeh Eyvani, George E. Sandusky, Michael Frieden, Harald Braun, Rudi Beyaert, Xiaoming He, Xinna Zhang, Chi Zhang, Sophie Paczesny, and Xiongbin Lu. 2020. “ST2 as Checkpoint Target for Colorectal Cancer Immunotherapy.” JCI INSIGHT 5 (9). doi:10.1172/jci.insight.136073.
Vancouver
1.
Van der Jeught K, Sun Y, Fang Y, Zhou Z, Jiang H, Yu T, et al. ST2 as checkpoint target for colorectal cancer immunotherapy. JCI INSIGHT. 2020;5(9).
IEEE
[1]
K. Van der Jeught et al., “ST2 as checkpoint target for colorectal cancer immunotherapy,” JCI INSIGHT, vol. 5, no. 9, 2020.
@article{8661450,
  abstract     = {{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.}},
  articleno    = {{e136073}},
  author       = {{Van der Jeught, Kevin and Sun, Yifan and Fang, Yuanzhang and Zhou, Zhuolong and Jiang, Hua and Yu, Tao and Yang, Jinfeng and Kamocka, Malgorzata M. and So, Ka Man and Li, Yujing and Eyvani, Haniyeh and Sandusky, George E. and Frieden, Michael and Braun, Harald and Beyaert, Rudi and He, Xiaoming and Zhang, Xinna and Zhang, Chi and Paczesny, Sophie and Lu, Xiongbin}},
  issn         = {{2379-3708}},
  journal      = {{JCI INSIGHT}},
  keywords     = {{MICROSATELLITE INSTABILITY,CELL,IL-33,EXPRESSION,INFLAMMATION,ENHANCEMENT,IMMUNITY}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{14}},
  title        = {{ST2 as checkpoint target for colorectal cancer immunotherapy}},
  url          = {{http://doi.org/10.1172/jci.insight.136073}},
  volume       = {{5}},
  year         = {{2020}},
}
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