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The function and dysfunction of memory CD8+ T cells in tumor immunity

Reading, JL; Gálvez-Cancino, F; Swanton, RC; Lladser, A; Peggs, K; Quezada, S; (2018) The function and dysfunction of memory CD8+ T cells in tumor immunity. Immunological Reviews , 283 (1) pp. 194-212. 10.1111/imr.12657. Green open access

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Abstract

The generation and maintenance of CD8+ T cell memory is crucial to long‐term host survival, yet the basic tenets of CD8+ T cell immunity are still being established. Recent work has led to the discovery of tissue‐resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8+ T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de‐repress the anti‐tumor response. However, the progress of immunotherapy is at a critical juncture, since the efficacy of immuno‐oncology agents remains confined to a fraction of patients and often fails to provide durable benefit. Unlocking the potential of immunotherapy requires the design of strategies that both induce a potent effector response and reliably forge stable, functional memory T cell pools capable of protecting from recurrence or relapse. It is therefore essential that basic and emerging concepts of memory T cell biology are rapidly and faithfully transposed to advance therapeutic development in cancer immunotherapy. This review highlights seminal and recent reports in CD8+ T cell memory and tumor immunology, and evaluates recent data from solid cancer specimens in the context of the key paradigms from preclinical models. We elucidate the potential significance of circulating effector cells poised downstream of neoantigen recognition and upstream of T cell dysfunction and propose that cells in this immunological ‘sweet spot’ may be key anti‐tumor effectors.

Type: Article
Title: The function and dysfunction of memory CD8+ T cells in tumor immunity
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/imr.12657
Publisher version: http://doi.org/10.1111/imr.12657
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Immunotherapy, Tumor Immunology, Memory T cell, Cancer, Oncology, Checkpoint Blockade
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10045477
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