Cytokine-overexpressing dendritic cells for cancer immunotherapy

Dendritic cells (DCs), the main type of antigen-presenting cells in the body, act as key mediators of adaptive immunity by sampling antigens from diseased cells for the subsequent priming of antigen-specific T and B cells. While DCs can secrete a diverse array of cytokines that profoundly shape the immune milieu, exogenous cytokines are often needed to maintain the survival, proliferation, and differentiation of DCs, T cells, and B cells. However, conventional cytokine therapies for cancer treatment are limited by their low therapeutic benefit and severe side effects. The overexpression of cytokines in DCs, followed by paracrine release or membrane display, has emerged as a viable approach for controlling the exposure of cytokines to interacting DCs and T/B cells. This approach can potentially reduce the necessary dose of cytokines and associated side effects to achieve comparable or enhanced antitumor efficacy. Various strategies have been developed to enable the overexpression or chemical conjugation of cytokines on DCs for the subsequent modulation of DC–T/B-cell interactions. This review provides a brief overview of strategies that enable the overexpression of cytokines in or on DCs via genetic engineering or chemical modification methods and discusses the promise of cytokine-overexpressing DCs for the development of new-generation cancer immunotherapy.