2020 Annual Meeting Poster: Kevin Van der Jeught

Home/2020 Annual Meeting Poster: Kevin Van der Jeught

2020 Annual Meeting Poster: Kevin Van der Jeught

2020 Annual Meeting Poster: Kevin Van der Jeught

Presentation Title: Title: ST2 as checkpoint target for colorectal cancer immunotherapy

Author Name(s): Kevin Van der Jeught1, Yifan Sun1, Yuanzhang Fang1, Zhuolong Zhou1, Hua Jiang2, Tao Yu1, Jinfeng Yang2, Malgorzata Maria Kamocka3, Kaman So4, Yujing Li1, Haniyeh Eyvani1, George E. Sandusky5, Michael Frieden1, Harald Braun6,7, Rudi Beyaert6,7, Xiaoming He8,9 , Xinna Zhang1,10, Chi Zhang1,4,10, Sophie Paczesny2,10*, Xiongbin Lu1,10*

Author Department and School Affiliation: 1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA; 2Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; 3Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA; 4Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; 5Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; 6VIB Center for Inflammation Research, Ghent, Belgium; 7Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; 8Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA; 9Marlene and Stewart Greenebaum Comprehensive Cancer Centre, University of Maryland, Baltimore, MD, USA; 10Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

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 the 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 interleukin-33 (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) are recruited into the tumor via CXCR3 expression and exacerbate the immunosuppressive TME, and that combination of ST2 depletion using ST2-knock out 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 the tumor-infiltrating ST2+TAMs. Together, our findings suggest that ST2 could serve as a potential checkpoint target for CRC immunotherapy.

|2020-09-04T16:40:37-04:00September 4th, 2020|Annual Meeting Posters|0 Comments

About the Author: Jessica Hall

Jessica Hall

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