Immunogenic clearance-mediated cancer vaccination

Abstract

With the advent of immune checkpoint blockades, current anticancer immunotherapy has resulted in unprecedented therapeutic efficacy in cancer patients. However, most tumors are unresponsive to immune checkpoint blockades, especially in highly immunosuppressive tumor microenvironments with a T-cell immunosurveillance deficiency. Here, a novel strategy, “immunogenic clearance,” based on activating the initial state of the cancer-immunity cycle, is proposed. This strategy aims to change cold tumors to hot ones by generating tumor-specific T cells. Achieving this requires not only inducing immunogenic cancer cell death but also enhancing cancer cell phagocytosis by dendritic cells, both of which play critical roles, leading to the activation of cross-priming. Unlike conventional cancer vaccines, which require ex vivo manipulation and known as tumor-specific antigens, this strategy can intrinsically expose various tumor neoantigens to the antigen-presenting cells and elicit potent T-cell-dependent antitumor activity. Thus “immunogenic clearance-mediated cancer vaccination” can be a promising therapeutic strategy in combination with immune checkpoint blockades.