Ghorani, E;
Quezada, SA;
(2018)
Chromatin regulation and immune escape.
Science
, 359
(6377)
pp. 745-746.
10.1126/science.aat0383.
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Abstract
Antigens expressed by cancer cells target them for elimination by tumor-infiltrating T cells (1). But, despite T cell recognition, advanced malignancies are often fatally progressive. T cell inhibitory (checkpoint) receptors, including programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4), contribute to immune suppression and dysfunction in tumors. Checkpoint inhibitors (CPIs) developed to block these pathways and derepress T cell activity have considerably improved outcomes for various cancer types. However, beyond certain rare and highly sensitive tumors (2), responses remain limited to a fraction of patients, and both primary and acquired resistance are frequently observed. Although much work has focused on defining and overcoming T cell–intrinsic inhibitory mechanisms, such as checkpoint expression, less is known about what regulates tumor cell sensitivity to T cell attack. On pages 801 and 770 of this issue, Miao et al. (3) and Pan et al. (4), respectively, find that chromatin remodeling pathways contribute to cancer cell immune resistance through control of interferon-stimulated gene (ISG) expression. This has implications for our understanding of why CPIs fail and suggests that targeting these pathways may enhance tumor immunotherapy.
Type: | Article |
---|---|
Title: | Chromatin regulation and immune escape |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1126/science.aat0383 |
Publisher version: | http://dx.doi.org/10.1126/science.aat0383 |
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: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, RESISTANCE, CANCER, IMMUNOTHERAPY, BLOCKADE, MELANOMA, SYSTEM, STAT5 |
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 |
URI: | https://discovery.ucl.ac.uk/id/eprint/10046489 |
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