TOX Regulates T Lymphocytes Differentiation and Its Function in Tumor

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Mar 27

PMID 36969216

Authors

Haiyue Niu

Huaquan Wang

Affiliations

Soon will be listed here.

Abstract

Thymocyte selection-associated high mobility group box protein (TOX) is expressed differently at all T lymphocytes development stages. Owing to more advanced scientific and technological means, including single-cell sequencing technology, heterogeneity of T lymphocytes and TOX has gradually been revealed. Further exploration of such heterogeneity will help us comprehend the developmental stage and functional characteristics of T lymphocytes in greater detail. Emerging evidence supports its regulation not only in exhausting, but also in activating T lymphocytes, thereby verifying TOX heterogeneity. TOX can be used not only as a latent intervention target for tumor diseases and chronic infections, and a therapeutic strategy for autoimmune diseases, but also as a critical factor predicting the drug response and overall survival of patients with malignant tumors.

Citing Articles

Population structure and selective signature analysis of local sheep breeds in Xinjiang, China based on high-density SNP chip.

Li Y, Li X, Han Z, Yang R, Zhou W, Peng Y Sci Rep. 2024; 14(1):28133.

PMID: 39548146 PMC: 11568293. DOI: 10.1038/s41598-024-76573-w.

Single-nuclei transcriptome analysis of channel catfish spleen provides insight into the immunome of an aquaculture-relevant species.

Aldersey J, Lange M, Beck B, Abernathy J PLoS One. 2024; 19(9):e0309397.

PMID: 39325796 PMC: 11426453. DOI: 10.1371/journal.pone.0309397.

Exhaustion of T cells after renal transplantation.

Wang X, Zhang J, Zhong P, Wei X Front Immunol. 2024; 15:1418238.

PMID: 39165360 PMC: 11333218. DOI: 10.3389/fimmu.2024.1418238.

TOX: a potential new immune checkpoint in cancers by pancancer analysis.

Qiu S, Lin W, Zhou Z, Hong Q, Chen S, Li J Discov Oncol. 2024; 15(1):354.

PMID: 39152366 PMC: 11329495. DOI: 10.1007/s12672-024-01236-1.

Single-nuclei sequencing of uterine serous carcinoma reveals racial differences in immune signaling.

Foley K, Adli M, Kim J Proc Natl Acad Sci U S A. 2024; 121(34):e2402998121.

PMID: 39133838 PMC: 11348309. DOI: 10.1073/pnas.2402998121.

References

Scott A, Dundar F, Zumbo P, Chandran S, Klebanoff C, Shakiba M . TOX is a critical regulator of tumour-specific T cell differentiation. Nature. 2019; 571(7764):270-274. PMC: 7698992. DOI: 10.1038/s41586-019-1324-y. View

Chen Y, Feng Z, Kuang X, Zhao P, Chen B, Fang Q . Increased lactate in AML blasts upregulates TOX expression, leading to exhaustion of CD8 cytolytic T cells. Am J Cancer Res. 2021; 11(11):5726-5742. PMC: 8640829. View

Watkins E, Antane J, Roberts J, Lorentz K, Zuerndorfer S, Dunaif A . Persistent antigen exposure via the eryptotic pathway drives terminal T cell dysfunction. Sci Immunol. 2021; 6(56). DOI: 10.1126/sciimmunol.abe1801. View

Lobbardi R, Pinder J, Martinez-Pastor B, Theodorou M, Blackburn J, Abraham B . TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia. Cancer Discov. 2017; 7(11):1336-1353. PMC: 5683427. DOI: 10.1158/2159-8290.CD-17-0267. View

Han H, Jeong S, Kim H, Kim H, Kim A, Kwon M . TOX-expressing terminally exhausted tumor-infiltrating CD8 T cells are reinvigorated by co-blockade of PD-1 and TIGIT in bladder cancer. Cancer Lett. 2020; 499:137-147. DOI: 10.1016/j.canlet.2020.11.035. View

Kim C, Jang M, Kim Y, Leem G, Kim K, Lee H . VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers. Sci Immunol. 2019; 4(41). DOI: 10.1126/sciimmunol.aay0555. View

Khan O, Giles J, McDonald S, Manne S, Ngiow S, Patel K . TOX transcriptionally and epigenetically programs CD8 T cell exhaustion. Nature. 2019; 571(7764):211-218. PMC: 6713202. DOI: 10.1038/s41586-019-1325-x. View

Blank C, Nicholas Haining W, Held W, Hogan P, Kallies A, Lugli E . Defining 'T cell exhaustion'. Nat Rev Immunol. 2019; 19(11):665-674. PMC: 7286441. DOI: 10.1038/s41577-019-0221-9. View

Maurice N, Berner J, Taber A, Zehn D, Prlic M . Inflammatory signals are sufficient to elicit TOX expression in mouse and human CD8+ T cells. JCI Insight. 2021; 6(13). PMC: 8410038. DOI: 10.1172/jci.insight.150744. View

10.

Dulmage B, Akilov O, Vu J, Falo L, Geskin L . Dysregulation of the TOX-RUNX3 pathway in cutaneous T-cell lymphoma. Oncotarget. 2019; 10(33):3104-3113. PMC: 6517103. DOI: 10.18632/oncotarget.5742. View

11.

Guo L, Li X, Liu R, Chen Y, Ren C, Du S . TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma. Cancer Med. 2020; 9(18):6694-6709. PMC: 7520261. DOI: 10.1002/cam4.3324. View

12.

Seo H, Chen J, Gonzalez-Avalos E, Samaniego-Castruita D, Das A, Wang Y . TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8 T cell exhaustion. Proc Natl Acad Sci U S A. 2019; 116(25):12410-12415. PMC: 6589758. DOI: 10.1073/pnas.1905675116. View

13.

Tessema M, Yingling C, Grimes M, Thomas C, Liu Y, Leng S . Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers. PLoS One. 2012; 7(4):e34850. PMC: 3319602. DOI: 10.1371/journal.pone.0034850. View

14.

Wang L, Bosselut R . CD4-CD8 lineage differentiation: Thpok-ing into the nucleus. J Immunol. 2009; 183(5):2903-10. PMC: 3387994. DOI: 10.4049/jimmunol.0901041. View

15.

Kim K, Park S, Park S, Kim G, Park S, Cho J . Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer. Genome Med. 2020; 12(1):22. PMC: 7048139. DOI: 10.1186/s13073-020-00722-9. View

16.

Liang C, Zhao Y, Chen C, Huang S, Deng T, Zeng X . Higher TOX Genes Expression Is Associated With Poor Overall Survival for Patients With Acute Myeloid Leukemia. Front Oncol. 2021; 11:740642. PMC: 8532529. DOI: 10.3389/fonc.2021.740642. View

17.

Maestre L, Garcia-Garcia J, Jimenez S, Reyes-Garcia A, Garcia-Gonzalez A, Montes-Moreno S . High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations. PLoS One. 2020; 15(2):e0229743. PMC: 7046285. DOI: 10.1371/journal.pone.0229743. View

18.

Yates K, Tonnerre P, Martin G, Gerdemann U, Al Abosy R, Comstock D . Epigenetic scars of CD8 T cell exhaustion persist after cure of chronic infection in humans. Nat Immunol. 2021; 22(8):1020-1029. PMC: 8600539. DOI: 10.1038/s41590-021-00979-1. View

19.

Alfei F, Kanev K, Hofmann M, Wu M, Ghoneim H, Roelli P . TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature. 2019; 571(7764):265-269. DOI: 10.1038/s41586-019-1326-9. View

20.

Veldman J, Placa J, Chong L, Terpstra M, Mastik M, van Kempen L . CD4+ T cells in classical Hodgkin lymphoma express exhaustion associated transcription factors TOX and TOX2: Characterizing CD4+ T cells in Hodgkin lymphoma. Oncoimmunology. 2022; 11(1):2033433. PMC: 8803106. DOI: 10.1080/2162402X.2022.2033433. View