Harnessing allogeneic CD4⁺ T cells to reinvigorate host endogenous antitumor immunity

Immune checkpoint blockade (ICB) therapies developed over the past decade have been among the most promising approaches for the treatment of patients with advanced cancers. However, the overall objective response rate of ICB therapy for various cancers remains insufficient. Hence, novel strategies are required to improve the efficacy of immunotherapy for advanced cancers. The graft-versus-tumor (GVT) effect, which reflects strong antitumor immunity, is known to occur after allogeneic hematopoietic stem cell transplantation (HSCT). The GVT effect is mainly caused by transplanted donor lymphocytes that recognize and react to distinct alloantigens on tumor cells. In contrast, transplanted allogeneic cells can, in some instances, induce endogenous antitumor immunity in recipients if the graft has been rejected. Because of this ability, allogeneic cells have also been used to induce endogenous antitumor immunity without HSCT, and their beneficial immune response is referred to as the "allogenic effect." Here, we review the usefulness of allogeneic cells, particularly allogeneic CD4⁺ T cells, in cancer immunotherapy by highlighting their unique potential to induce host endogenous antitumor immunity.