The janus face of il-33 signaling in tumor development and immune escape

Mi Ran Choi, Jeffrey A. Sosman, Bin Zhang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Interleukin-33 (IL-33), a member of the IL-1 cytokine family, plays a critical role in main-taining tissue homeostasis as well as pathological conditions, such as allergy, infectious disease, and cancer, by promoting type 1 and 2 immune responses. Through its specific receptor ST2, IL-33 exerts multifaceted functions through the activation of diverse intracellular signaling pathways. ST2 is expressed in different types of immune cells, including Th2 cells, Th1 cells, CD8+ T cells, regulatory T cells (Treg), cytotoxic NK cells, group 2 innate lymphoid cells (ILC2s), and myeloid cells. During cancer initiation and progression, the aberrant regulation of the IL-33/ST2 axis in the tumor microenvironment (TME) extrinsically and intrinsically mediates immune editing via modulation of both innate and adaptive immune cell components. The summarized results in this review suggest that IL-33 exerts dual-functioning, pro-as well as anti-tumorigenic effects depending on the tumor type, expression levels, cellular context, and cytokine milieu. A better understanding of the distinct roles of IL-33 in epithelial, stromal, and immune cell compartments will benefit the development of a targeting strategy for this IL-33/ST2 axis for cancer immunotherapy.

Original languageEnglish (US)
Article number3281
Issue number13
StatePublished - Jul 1 2021


  • Cancer immunotherapy
  • Cellular context
  • IL-33
  • Immune editing
  • ST2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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