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Comparative transcriptome analysis reveals distinct genetic modules associated with Helios expression in intratumoral regulatory T cells

2018; National Academy of Sciences; Volume: 115; Issue: 9 Linguagem: Inglês

10.1073/pnas.1720447115

1091-6490

Kathleen B. Yates, Kevin Bi, W. Nicholas Haining, Harvey Cantor, Hye‐Jung Kim,

Immunotherapy and Immune Responses

Significance Regulatory T cells (Tregs) play a critical role in inflammatory, autoimmune, and antitumor immune responses. Increased expression of transcription factor Helios by tumor-infiltrating Tregs can enhance immune-suppressive activity, while deletion of Helios promotes an effector T helper (Th) cell phenotype that can contribute to the host antitumor immune response. We report that chronic inflammatory conditions of tumors induce Helios-deficient Tregs to express increased levels of genes associated with T cell activation and Th cell differentiation. Helios-dependent changes in gene expression are restricted to tumor sites and not observed in peripheral lymphoid tissues. We suggest that Helios-deficient Tregs that recognize tumor-associated self-antigens may become unstable in the tumor microenvironment and undergo reprogramming into effector T cells that can inhibit tumor growth.