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Transcriptional regulator SATB1 limits CD8⁺ T cell population expansion and effector differentiation in chronic infection and cancer

Kallies and colleagues examine the role of the chromatin regulator SATB1 in CD8⁺ T cell differentiation during viral infection and cancer. They show that SATB1 is a negative regulator of exhausted CD8⁺ T cell expansion and effector differentiation.

Leonie Heyden
Lisa Rausch
Axel Kallies
Research27 Oct 2025
Nature Immunology

Volume: 26, P: 2312-2327
Lymph nodes fuel KLF2-dependent effector CD8⁺ T cell differentiation during chronic infection and checkpoint blockade

Here the authors show a function for lymph nodes in the maintenance of effector T cell differentiation and function during chronic infection and checkpoint blockade, identifying a spatial component in the regulation of exhausted T cell fitness.

Carlson Tsui
Leonie Heyden
Axel Kallies
Research15 Sept 2025
Nature Immunology

Volume: 26, P: 1752-1765
Early precursor T cells establish and propagate T cell exhaustion in chronic infection

The developmental timing for exhaustion is still obscure. Kallies and colleagues demonstrate that CD8⁺ T cell ‘exhaustion’ actually begins in the less-differentiated TCF1⁺ ‘precursor’ T cell pool during chronic viral infections.

Daniel T. Utzschneider
Sarah S. Gabriel
Axel Kallies
Research24 Aug 2020
Nature Immunology

Volume: 21, P: 1256-1266
Lymph-node-derived stem-like but not tumor-tissue-resident CD8⁺ T cells fuel anticancer immunity

Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

Sharanya K. M. Wijesinghe
Lisa Rausch
Axel Kallies
Research29 Jul 2025
Nature Immunology

Volume: 26, P: 1367-1383
Nutrient metabolism shapes epigenetic landscape of T cells

CD8⁺ T cell exhaustion is defined by a unique transcriptional and epigenetic profile that is important to understand for the generation of immunotherapies to treat cancer. Research now shows how this profile can be regulated by T cells switching their nutrient sources.

Annika Poch
Daniel T. Utzschneider
News & Views31 Jan 2025
Nature Immunology

Volume: 26, P: 340-341
T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion

During chronic infection, pathogen-specific CD8⁺ T cells are thought to terminally differentiate into exhausted cells. However, Zehn and colleagues show that T cells with memory-like properties are generated during such infections.

Daniel T Utzschneider
Amandine Legat
Dietmar Zehn
Research05 May 2013
Nature Immunology

Volume: 14, P: 603-610
MYB orchestrates T cell exhaustion and response to checkpoint inhibition

CD62L⁺ precursors of exhausted T cells retain long-term proliferative potential, multipotency and repopulation capacity, and the transcription factor MYB is essential for the development and function of this population of cells.

Carlson Tsui
Lorenz Kretschmer
Axel Kallies
ResearchOpen Access17 Aug 2022
Nature

Volume: 609, P: 354-360
Antigen-driven EGR2 expression is required for exhausted CD8⁺ T cell stability and maintenance

Exhausted T cells arise when chronic activation triggers functional defects. Here the authors show that chronic antigenic stimulation in both tumour and infection models induces the expression of EGR2, which drives and stabilises exhausted cell epigenetic and transcriptional identity.

Mayura V. Wagle
Stephin J. Vervoort
Ian A. Parish
ResearchOpen Access13 May 2021
Nature Communications

Volume: 12, P: 1-15
T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

Chronic viral infections and malignant tumours are associated with the development of T cells that have an 'exhausted' phenotype and that are thought to be severely functionally impaired. In this Opinion article, the authors propose that the exhausted phenotype is actually a functional adaptation to cause minimal tissue damage while still mediating a critical level of pathogen control.

Daniel E. Speiser
Daniel T. Utzschneider
Dietmar Zehn
Reviews26 Sept 2014
Nature Reviews Immunology

Volume: 14, P: 768-774
NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions

NK cell tolerance to self-MHCI levels is calibrated during their development. Here the authors show that this tolerance is overcome by an inflammatory environment and that NLRC5 protects T cells from NK cell-mediated elimination by maintaining high MHCI expression.

Kristina Ludigs
Camilla Jandus
Greta Guarda
ResearchOpen Access10 Feb 2016
Nature Communications

Volume: 7, P: 1-10
Precursor exhausted T cells: key to successful immunotherapy?

Recent studies have revealed a specialized population of ‘exhausted’ CD8⁺ T cells that expands on immune checkpoint blockade therapy for cancer and may explain how T cell responses are maintained in chronic conditions. Here, the authors describe their phenotypic, developmental and functional characteristics and why they should be harnessed for successful immunotherapy.

Axel Kallies
Dietmar Zehn
Daniel T. Utzschneider
Reviews07 Oct 2019
Nature Reviews Immunology

Volume: 20, P: 128-136
TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection

TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infections.

Francesca Alfei
Kristiyan Kanev
Dietmar Zehn
Research17 Jun 2019
Nature

Volume: 571, P: 265-269
Mouse guanylate-binding proteins of the chromosome 3 cluster do not mediate antiviral activity in vitro or in mouse models of infection

Mouse guanylate binding proteins of the chromosome 3 cluster (mGBPchr3) do not mediate potent antiviral activity against different human or mouse viruses in vitro and in vivo.

Melkamu B. Tessema
Shouya Feng
Patrick C. Reading
ResearchOpen Access25 Aug 2024
Communications Biology

Volume: 7, P: 1-17

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