IL-27 in tumor immunity and immunotherapy

Inflammation has a central role in cancer progression. Metastatic tumors arise at sites of chronic inflammation, and tumors or tumor-infiltrating immune cells produce inflammatory mediators. By contrast, natural killer (NK) cells and cytotoxic T cells (CTLs) help eliminate premalignant lesions and limit the rate of tumor metastasis. Interleukin (IL)-27 is an IL-12 family cytokine chiefly produced by antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages, and alone or in combination with other cytokines, IL-27 boosts antitumor immunity by contributing to the development of NK cells and CTLs - a central immnunomodulatory effect - and by exerting potent antiangiogenic and antimetastatic activities, a local antitumor effect. In this review, we argue that by virtue of its rate-limiting functions in innate and adaptive immune responses, modulating IL-27 holds considerable promise for future cancer immunotherapy.