Interleukin-1β: Friend or foe for gastrointestinal cancers

Abstract

Gastrointestinal (GI) cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality, especially in the colorectum, esophagus, stomach, and liver. Interleukin-1β (IL-1β) is a leukocytic pyrogen recognized as a tumor progression-related cytokine. IL-1β secretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3, inflammasome formation, and activation of IL-1 converting enzyme. Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments, promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo. The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types. However, as a leukocytic pro-inflammatory cytokine, IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers. This editorial discusses the up-to-date roles of IL-1β in GI cancers, including underlying mechanisms and downstream signaling pathways. Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

Keywords: Cancer; Gastrointestinal tract; Inflammation; Interleukin-1β; Tumor microenvironment

Core Tip: Interleukin-1β (IL-1β) is a pro-inflammatory cytokine primarily secreted by leukocytes to activate the immune response at the site of infection or inflammation. As tumor-promoting inflammation is one of the cancer hallmarks, IL-1β then plays central roles in tumor-promoting activities in many cancers, including cancers of the gastrointestinal tract. On the other hand, by activating and recruiting immune cells into the tumor microenvironments, IL-1β also has anti-tumor effects depending on the subtypes of immune cells that respond and infiltrate into the tumor site. Whether it could be a promising target for future therapeutic development is then discussed in this article.