Interleukin-33 in Malignancies: Friends or Foes?

Abstract

The human Interleukin-33 (IL-33), a member of the IL-1 family, is the cytokine as a cell endogenous alarmin, released by damaged or necrotic barrier cells (endothelial and epithelial cells). The signal transduction of IL-33 relies on recognition and interaction with specific receptor ST2, mainly expressed in immune cells. In both innate and adoptive immunity, IL-33 regulates the homeostasis in response to stress from within/out the microenvironment. Various, even negative biofunctions of IL-33 pathways have now been widely verified in pathogenesis among immunological mechanisms, like Th2-related immune-stimuli, inflammation/infection-induced tissue protectors. A larger versatility in studies of IL-33 on malignancies now focuses on: (1) promoting myeloid-derived suppressor cells (MDSC), (2) intervention toward CD8+ T, Natural Killer (NK) cell infiltration, group 2 innate lymphoid cells (ILC2) proliferation, dendritic cells (DC) activation, and (3) inhibiting tumor growth and/or further metastasis as an immunoadjuvant. Although IL-33 functioned pro-tumorigenically in various cancers, for some cancer types the findings so far are controversial. This review begins from a summarized introduction of IL-33, to its remarkable implications and molecular transduction pathway in malignant neoplasms, ends with latest inspiration for IL-33 in treatment.

Colorectal carcinoma: Evaluation of systemic values of interleukin-1 and interleukin-33 in patients with and without thrombocytosis

“…Previous studies confirmed important role of IL-33 in CRC pathogenesis 13,14 . It is known that IL-33 activates core stem cell genes, recruits macrophages into the cancer microenvironment and stimulates them to produce prostaglandin E2, which all promote carcinogenesis of CRC and metastasis of cancers 16,30 .…”

“…Recent study revealed that IL-33 by biding to its receptor ST2 inhibits host anti-tumor immunity, remodels tumor stroma and enhances angiogenesis, thereby promoting the development of CRC 15 . Patients with metastatic CRC, with higher expression of IL-33 in cancer tissues were significantly associated with poorer survival 14,16 . IL…”

“…Interleukin (IL)-33, an IL-1 family member, plays an essential role in the regulation of immune response after cellular stress or damage 13,14 . Recent study revealed that IL-33 by biding to its receptor ST2 inhibits host anti-tumor immunity, remodels tumor stroma and enhances angiogenesis, thereby promoting the development of CRC 15 .…”

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression

“…Astrocyte-derived IL-33 also promote synapse homeostasis by microglia during early CNS development 58 . In addition, there is emerging data to suggest a pro-tumorigenic role for IL-33 in various cancers 59 , including glioma, where IL-33 expression correlates with poor prognosis 60,61 and increased tumor growth with observed macrophage infiltration in a rat glioma model 62 .…”

Immune-Stromal Score Signature: Novel Prognostic Tool of the Tumor Microenvironment in Lung Adenocarcinoma

“…Previous studies have suggested that IL-2 is involved in antitumor T cell infiltration, increasing the efficacy of immunotherapy ( 22 ). IL-33 also promotes myeloid-derived suppressor cells (MDSCs) and interferes with CD8+ T and natural killer (NK) cell infiltration ( 23 ). These studies have suggested that certain cytokines are involved in antitumor immune pathways, potentially elucidating the mechanisms associated with prognosis.…”