Details

Autor(en) / Beteiligte

• Van der Jeught, Kevin
• Sun, Yifan
• Fang, Yuanzhang
• Zhou, Zhuolong
• Jiang, Hua
• Yu, Tao
• Yang, Jinfeng
• Kamocka, Malgorzata M
• So, Ka Man
• Li, Yujing
• Eyvani, Haniyeh
• Sandusky, George E
• Frieden, Michael
• Braun, Harald
• Beyaert, Rudi
• He, Xiaoming
• Zhang, Xinna
• Zhang, Chi
• Paczesny, Sophie
• Lu, Xiongbin

Titel

ST2 as checkpoint target for colorectal cancer immunotherapy

Ist Teil von

• JCI insight, 2020-05, Vol.5 (9)

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.