TOX is a critical regulator of tumour-specific T cell differentiation.

ABSTRACT: Tumour-specific CD8 T cell dysfunction is a differentiation state that is distinct from the functional effector or memory T cell states^1-6. Here we identify the nuclear factor TOX as a crucial regulator of the differentiation of tumour-specific T (TST) cells. We show that TOX is highly expressed in dysfunctional TST cells from tumours and in exhausted T cells during chronic viral infection. Expression of TOX is driven by chronic T cell receptor stimulation and NFAT activation. Ectopic expression of TOX in effector T cells in vitro induced a transcriptional program associated with T cell exhaustion. Conversely, deletion of Tox in TST cells in tumours abrogated the exhaustion program: Tox-deleted TST cells did not upregulate genes for inhibitory receptors (such as Pdcd1, Entpd1, H

SUBMITTER: Scott AC 

PROVIDER: S-EPMC7698992 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature