![]() Nicholas Haining is a physician–scientist and Vice-President for Discovery Oncology and Immunology at Merck Research Laboratories. His research interests include neoadjuvant immunotherapies, targeted and biological response modifiers, and prognostic markers for cancer immunotherapies. He is Professor of Haematology/Oncology at the University of Regensburg, Germany, and received an MBA degree from the University of Warwick, UK. Blank is a medical oncologist and principal investigator at the Netherlands Cancer Institute. Recent studies have also highlighted an important role for the transcriptional regulator TOX in driving the epigenetic enforcement of exhaustion, but key questions remain about the potential to reverse the epigenetic programme of exhaustion and how this might affect the persistence of T cell populations.Ĭhristian U. These TCF1 + cells are considered by some to have stem cell-like properties akin to memory T cell populations, but the developmental relationships are unclear at present. Their responses highlight the dichotomy between terminally differentiated exhausted T cells that are TCF1 – and the self-renewing TCF1 + population from which they derive. In this Viewpoint article, 18 experts in the field tell us what exhaustion means to them, ranging from complete lack of effector function to altered functionality to prevent immunopathology, with potential differences between cancer and chronic infection. Understanding the features of and pathways to exhaustion has crucial implications for the success of checkpoint blockade and adoptive T cell transfer therapies. ‘T cell exhaustion’ is a broad term that has been used to describe the response of T cells to chronic antigen stimulation, first in the setting of chronic viral infection but more recently in response to tumours. Nature Reviews Immunology volume 19, pages 665–674 ( 2019) Cite this article
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