| 2019 |
TOX2 cooperates with TOX and NR4A transcription factors downstream of NFAT (in the absence of AP-1) to drive the transcriptional program of CD8+ T cell exhaustion; Tox/Tox2 double-knockout CAR TILs showed increased cytokine expression, decreased inhibitory receptor expression, and increased chromatin accessibility at NFκB/bZIP motif-enriched regions; positive regulatory loops between TOX and NR4A were identified. |
CAR T cell mouse model, CRISPR double-knockout (Tox DKO), ATAC-seq, transcriptional analysis, genetic epistasis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
31152140
|
| 2019 |
TOX2 is required for T follicular helper (Tfh) cell differentiation: ectopic expression of Tox2 was sufficient to drive Bcl6 expression and Tfh development; Tox2 ChIP-seq showed direct binding to Bcl6 and other Tfh-associated loci; Tox2 binding was associated with increased chromatin accessibility (ATAC-seq); Tox2-/- mice had defective Tfh differentiation, and combined Tox2/Tox deficiency abolished Tfh differentiation, establishing a Tox2-Bcl6 feed-forward loop. |
Tox2-/- mouse model, ectopic expression, genome-wide ChIP-seq, ATAC-seq, epistasis with Tox |
Immunity |
High |
31732165
|
| 2014 |
TOX2 controls human NK cell development by directly upregulating transcription of TBX21 (T-BET), acting upstream of TBX21; TOX2 knockdown hindered early NK cell developmental transitions, and overexpression of T-BET rescued TOX2 knockdown phenotypes; TOX2 acted independently of ETS-1. |
shRNA gene silencing, overexpression in CD34+ cord blood cells, rescue experiment with T-BET overexpression, in vitro NK cell differentiation assay |
Blood |
High |
25352127
|
| 2021 |
Tox2 is required for maintenance of germinal center (GC) TFH cells and generation of memory TFH cells; Tox2 overexpression maintained TFH-associated gene expression and inhibited spontaneous conversion of GC TFH cells into TH1-like cells; Tox2-deficient mice showed impaired secondary TFH expansion upon reimmunization. |
Tox2-/- mouse model, Tox2 overexpression in human GC TFH cells, reimmunization/secondary infection challenge, transcriptional analysis |
Science advances |
High |
34623911
|
| 2023 |
TOX2 mediates oncogenesis in Natural Killer/T-cell lymphoma (NKTL) downstream of RUNX3, which regulates TOX2 transcription by binding to active elements of its super-enhancer; TOX2 knockdown or CRISPR-dCas9 interference of its super-enhancer impaired cell proliferation, survival, and colony formation in vitro and tumor formation in vivo; PRL-3 (metastasis-associated phosphatase) was identified and validated as a key downstream effector of TOX2. |
shRNA knockdown, CRISPR-dCas9 SE interference, luciferase reporter assay, ChIP-PCR, in vivo xenograft model |
Molecular cancer |
Medium |
37032358
|
| 2023 |
In human CAR T cells, TOX2 (in contrast to TOX) promotes central memory T cell (TCM) differentiation: TOX2 knockdown decreased TCM percentage and reduced proliferation; TOX2 bound to promoters of numerous TCM-associated genes; increased TET2 loss led to increased TOX2 expression and chromatin accessibility at TOX2 locus. |
TOX2 knockdown, ChIP-seq (TOX2 at TCM gene promoters), ATAC-seq, flow cytometry, gene expression analysis in human CAR T cells |
Science advances |
Medium |
37467321
|
| 2024 |
Tox2 is required for metabolic adaptation and tissue residency of gut ILC3: Tox2 deficiency decreased ILC3 specifically in gut (not central sites) and impaired control of Citrobacter rodentium infection; single-cell transcriptomics revealed decreased Hexokinase-2 expression in Tox2-deficient ILC3; Tox2-/- ILC3 showed decreased glycolytic capacity for protein translation; ectopic Hexokinase-2 expression rescued Tox2-/- ILC3 defects; hypoxia and IL-17A each induced Tox2 expression in ILC3. |
Tox2-/- mouse model, single-cell transcriptional profiling, ectopic Hexokinase-2 rescue, infection challenge, glycolysis assay |
Immunity |
High |
38677292
|
| 2024 |
TOX2 nuclear-cytosol translocation is regulated by deacetylation cooperatively mediated by Sirt1 and kinase TBK1; nuclear TOX and TOX2 form a protein complex and repress HAVCR2 (TIM3) promoter activity by recruiting corepressor LCOR and deacetylase HDAC3; radiation damage induced TOX2 nuclear translocation and decreased Sirt1, TIM3, and caspase 1 expression; knockdown of TOX2, TOX, or LCOR, or HDAC3 inhibition induced leukemic cell apoptosis in vitro and reduced tumor growth in vivo. |
Co-immunoprecipitation (protein complex), subcellular fractionation/localization, luciferase promoter assay, shRNA knockdown, HDAC3 inhibitor, in vivo xenograft model |
Cell death and differentiation |
Medium |
39080376
|
| 2025 |
Genome-wide binding sites of TOX2 in primary human CD8 T cells were mapped using the Calling Cards transposon-based method; TOX2 binding sites in CD8 T cells were identified and associated with exhaustion and memory gene programs. |
Calling Cards transposon-based TF mapping (chromatin binding), integration with multi-omic sequencing in primary human CD8 T cells |
bioRxivpreprint |
Medium |
bio_10.1101_2025.10.09.681414
|