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Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity

2016; National Academy of Sciences; Volume: 113; Issue: 22 Linguagem: Inglês

10.1073/pnas.1604765113

1091-6490

Hidetoshi Nakagawa, Jessica M. Sido, Edwin E. Reyes, Valerie Kiers, Harvey Cantor, Hye Jung Kim,

Immunotherapy and Immune Responses

Significance Depletion or inhibition of regulatory T cells (Tregs) has been associated with increased effector T-cell activation that may enhance antitumor responses. A potentially more effective strategy depends on induction of lineage instability that allows conversion of intratumoral but not systemic Tregs into effector T cells (Teffs). We show that targeted deletion of the Helios transcription factor within CD4 Tregs promotes instability and effector cell conversion of Tregs in tumors and increased antitumor immunity. Ab-dependent ligation of Treg surface receptors that diminishes Helios expression can also induce intratumoral Treg conversion. These findings indicate that targeting of signaling pathways that reduce Helios expression by intratumoral Tregs may represent a potentially robust approach to cancer immunotherapy.