Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation

• DOI: 10.1016/j.xcrm.2024.101441
• Publication Date: 2024-02-29T15:37:27Z
• Authors: Shuvam M. Chaudhuri; Samuel E. Weinberg; Dongmei Wang; Lenore K. Yalom; Elena Montauti; Radhika Iyer; Amy Y. Tang; Manuel A. Torres ...; Jian Shen; Nikita L. Mani; Shengnan Wang; Kun Liu; Weiyuan Lu; Triet M. Bui; Laura D. Manzanares; Zeinab Dehghani; Ching Man Wai; Beixue Gao; Juncheng Wei; Feng Yue; Weiguo Cui; Benjamin D. Singer; Ronen Sumagin; Yana Zhang; Deyu Fang
• Keywords: Mediator; Cancer Immunotherapy

While immunotherapy has revolutionized cancer treatment, its safety been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (Treg) cell function specifically in the tumor microenvironment. Treg cell-specific MED1 deletion does not predispose mice to autoimmunity or excessive inflammation. In contrast, promotion of growth because terminal differentiation effector cells tumor. Suppression these terminally differentiated sufficient eliciting antitumor immunity. Both human and murine experience divergent paths tumors matched tissues with non-malignant Collectively, identify a pathway promoting subset specific demonstrate suppression immunity absence autoimmune consequences.