Interleukin-21 as an adjuvant in cancer immunotherapy: Current advances and future directions

Immunotherapy has revolutionized cancer treatment. However, it's well-recognized that a considerable proportion of patients fail to benefit from immunotherapy, and to improve immunotherapy response is clinically urgent. Insufficient immune infiltration and immunosuppressive tumor microenvironments (TME) are main contributors to immunotherapy resistance. Thus sustaining functional self-renewal capacity for immune cells and subverting immune-suppressive signals are potential strategies for boosting the efficacy of immunotherapy. Interleukin-21 (IL-21), a crucial cytokine, which could enhance cytotoxic function of immune cells and reduces immunosuppressive cells enrichment in TME, shows promising orientations as an immunoadjuvant in tumor immunotherapy. This review focuses on IL-21 in cancer treatment, including function and mechanisms of IL-21, preclinical and clinical studies, and future directions for IL-21-assisted therapies.