In this study, we discovered that deletion of gp96 from committed Tregs in mice resulted in complete blockade of LFA-1–dependent infiltration of Tregs into the TME and compromised the activation of effector Tregs, leading to enhanced CD8+ TIL activation, hindrance of IL-2–dependent, TOX-mediated T cell exhaustion, and a superior ability to eradicate multiple tumor types without inducing autoimmunity. The gene discussed is HSP90B1; the disease is Autoimmunity.