Nuclear Coregulatory Complexes in Tregs as Targets to Promote Anticancer Immune Responses

Abstract

T-regulatory (Treg) cells display considerable heterogeneity in their responses to various cancers. The functional differences among this cell type are heavily influenced by multiprotein nuclear complexes that control their gene expression. Many such complexes act mechanistically by altering epigenetic profiles of genes important to Treg function, including the forkhead P3 (Foxp3) transcription factor. Complexes that form with certain members of the histone/protein deacetylase (HDAC) class of enzymes, like HDACs 1, 2, and 3, along with histone methyltransferase complexes, are important in the induction and stabilization of Foxp3 and Treg identity. The functional behavior of both circulating and intratumoral Tregs greatly impacts the antitumor immune response and can be predictive of patient outcome. Thus, targeting these regulatory complexes within Tregs may have therapeutic potential, especially in personalized immunotherapies.

GPRASP1 is a candidate anti‐oncogene and correlates with immune microenvironment and immunotherapeutic efficiency in head and neck cancer

“…22 Tregs, a subpopulation of helper T cells, suppress the activation of immune cell types (such as CD4 T cells and CD8 T cells), limit immune responses, and maintain immune self-tolerance. 23 In our study, the CIBERSORTx tool, and ssGSEA algorithm found that B cells, CD8 T cells, NK cells, and TIL were more abundant in GPRASP1 high subgroup. Correlation analysis further revealed that GPRASP1 expression was significantly positively associated with B cells, CD4 T cells, CD8 T cells, and TIL, whereas significantly negatively correlated with Tregs.…”

“…TIL, refers to lymphocytes surrounding the tumor, represents the ability of tumor‐related immune responses, and can predict the therapeutic effect of immunotherapy 22 . Tregs, a subpopulation of helper T cells, suppress the activation of immune cell types (such as CD4 T cells and CD8 T cells), limit immune responses, and maintain immune self‐tolerance 23 . In our study, the CIBERSORTx tool, and ssGSEA algorithm found that B cells, CD8 T cells, NK cells, and TIL were more abundant in GPRASP1 high subgroup.…”

HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients’ T-cells

“…By contrast, although the non-Tax-target gene FOXP3 also significantly increased upon HDACi treatment, expression of FOXP3 remained ca. two logarithmic orders lower than expression of the target genes ( Supplementary Figure S3B , lower panel ( 54 )). These findings on the transcriptional level in MT-2 cells ( Figure 4C, D ; Supplementary Figure S3B ) paralleled the results from the transiently transfected Jurkat T-cells ( Figure 3C, D ; Supplementary Figure S2B ).…”