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Nat Rev Immunol. 2019 Oct 7. doi: 10.1038/s41577-019-0223-7. [Epub ahead of print]

Precursor exhausted T cells: key to successful immunotherapy?

Author information

1
Department of Microbiology & Immunology Melbourne, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia. axel.kallies@unimelb.edu.au.
2
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
3
Department of Microbiology & Immunology Melbourne, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia. daniel.utzschneider@unimelb.edu.au.

Abstract

Cytotoxic T cell immunity in response to chronic infections and tumours is maintained by a specialized population of CD8+ T cells that exhibit hallmarks of both exhausted and memory cells and give rise to terminally differentiated exhausted effector cells that contribute to viral or tumour control. Importantly, recent work suggests these cells, which we refer to as 'precursor exhausted' T (TPEX) cells, are responsible for the proliferative burst that generates effector T cells in response to immune checkpoint blockade targeting programmed cell death 1 (PD1), and increased TPEX cell frequencies have recently been linked to increased patient survival. We believe the recent discovery of TPEX cells not only represents a paradigm shift in our understanding of the mechanisms that maintain CD8+ T cell responses in chronic infections and tumours but also opens up unexpected avenues for the development of new and innovative therapeutic approaches. In this Opinion article, we discuss the differentiation and function of TPEX cells and suggest that targeting these cells may be key for successful immunotherapy.

PMID:
31591533
DOI:
10.1038/s41577-019-0223-7

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