The double-edged sword of TOX: orchestrating T cell exhaustion and epigenetic remodeling in the tumor microenvironment
Year: 2026
Type: review
Abstract: The capacity to profoundly change chromatin domains and in turn drive or inhibit gene expression makes chromatin modulators a powerful tool adopted to regulate crucial steps during development and cell lineage specification. These proteins can however be as well engaged to irreversibly reprogram cells toward pathological outcomes such as cancer. An example of such chromatin remodelers is the family of Thymocyte-selection associated high mobility box proteins (TOX), which has rather pleiotropic functions during development and in cancer. In light of the most recent findings, this review gives an overview on the many different roles played by TOX family of proteins in physiological processes, and of the context-dependent effects that TOX induces in a variety of tumors. A particular attention is given to the contribution of TOX to the mechanism of T cell-exhaustion and to the "exhaustion lock" - no longer viewed as a dysfunctional immunological program but rather as a sophisticated strategy evolved by the immune system to keep control during events of chronic stress. The therapeutic potentials of TOX as valuable biomarker and target in cancer and immunotherapy as well as in adoptive cell therapies are also discussed.
Source: Frontiers in Immunology
Institutions: Istituto Oncologico Veneto, University of Padua
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221595586