Peripheral Tolerance Mechanisms in Cancer Immunity: Friend or Foe

Peripheral immune tolerance plays a dual role in cancer immunity, acting as both a guardian and an accomplice. Under normal conditions, it prevents autoimmunity by maintaining self-tolerance through mechanisms such as T-cell anergy, deletion, regulatory T-cell (Treg) suppression, and tolerogenic antigen presentation. However, tumors exploit these same pathways to evade immune destruction. By inducing Tregs, expressing inhibitory checkpoints like PD-L1, and promoting tolerogenic dendritic cells, cancers suppress effector T-cell activity and create an immunosuppressive microenvironment. This immune evasion hinders tumor antigen recognition and limits the effectiveness of antitumor responses and immunotherapies. Understanding how peripheral tolerance is subverted by tumors has led to therapeutic breakthroughs, notably checkpoint blockade therapies that reverse tolerance and restore immune activation. Balancing the restoration of antitumor immunity while preventing autoimmunity remains a central challenge in cancer immunotherapy research