Gato-Canas, M;
Zuazo, M;
Arasanz, H;
Ibanez-Vea, M;
Lorenzo, L;
Fernandez-Hinojal, G;
Vera, R;
... Escors, D; + view all
(2017)
PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity.
Cell Reports
, 20
(8)
pp. 1818-1829.
10.1016/j.celrep.2017.07.075.
Preview |
Text
Escors_1-s2.0-S2211124717310689-main.pdf - Published Version Download (4MB) | Preview |
Abstract
PDL1 blockade produces remarkable clinical responses, thought to occur by T cell reactivation through prevention of PDL1-PD1 T cell inhibitory interactions. Here, we find that PDL1 cell-intrinsic signaling protects cancer cells from interferon (IFN) cytotoxicity and accelerates tumor progression. PDL1 inhibited IFN signal transduction through a conserved class of sequence motifs that mediate crosstalk with IFN signaling. Abrogation of PDL1 expression or antibody-mediated PDL1 blockade strongly sensitized cancer cells to IFN cytotoxicity through a STAT3/caspase-7-dependent pathway. Moreover, somatic mutations found in human carcinomas within these PDL1 sequence motifs disrupted motif regulation, resulting in PDL1 molecules with enhanced protective activities from type I and type II IFN cytotoxicity. Overall, our results reveal a mode of action of PDL1 in cancer cells as a first line of defense against IFN cytotoxicity.
| Type: | Article |
|---|---|
| Title: | PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2017.07.075 |
| Publisher version: | http://dx.doi.org/10.1016/j.celrep.2017.07.075 |
| Language: | English |
| Additional information: | © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, I INTERFERON, ACQUIRED-RESISTANCE, PD-1 BLOCKADE, T-CELLS, CANCER, MELANOMA, SENESCENCE, EXPRESSION, RECEPTOR, CONTRIBUTES |
| 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 |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1571631 |
Archive Staff Only
 |
View Item |
