The Impact of Tregs on the Anticancer Immunity and the Efficacy of Immune Checkpoint Inhibitor Therapies

Although cancers arise from genetic mutations enabling cells to proliferate uncontrollably, they cannot thrive without failure of the anticancer immunity due in a large part to the tumor environment's influence on effector and regulatory T cells. The field of immune checkpoint inhibitor (ICI) therapy for cancer was born out of the fact that tumor environments paralyze the immune cells that are supposed to clear them by activating the immune checkpoint molecules such as PD-1. While various subsets of effector T cells work collaboratively to eliminate cancers, Tregs enriched in the tumor environment can suppress not only the native anticancer immunity but also diminish the efficacy of ICI therapies. Because of their essential role in suppressing autoimmunity, various attempts to specifically deplete tumor-associated Tregs are currently underway to boost the efficacy of ICI therapies without causing systemic autoimmune responses. A better understanding the roles of Tregs in the anti-cancer immunity and ICI therapies should provide more specific targets to deplete intratumoral Tregs. Here, we review the current understanding on how Tregs inhibit the anti-cancer immunity and ICI therapies as well as the advances in the targeted depletion of intratumoral Tregs.

Automated summary

Cancer arises from genetic mutations allowing cells to proliferate uncontrollably, but the failure of anticancer immunity, influenced by the tumor environment's impact on T cells, is essential for cancer survival. Immune checkpoint inhibitor therapy was developed to combat the immune paralysis induced by tumor environments, specifically by targeting molecules like PD-1. While effector T cells work to eliminate cancers, Tregs in the tumor environment suppress native anticancer immunity and reduce the efficacy of ICI therapies. Targeted efforts to deplete tumor-associated Tregs are underway to enhance ICI therapy effectiveness without causing systemic autoimmune responses. Understanding the roles of Tregs in anti-cancer immunity and ICI therapies can lead to more precise targeting of intratumoral Tregs.