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PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity
Open accessAbstract
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.
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Metadata
- Authors
- Gato-Cañas, M., Zuazo, M., Arasanz, H., Ibañez-Vea, M., Lorenzo, L., Fernandez-Hinojal, G., Vera, R., Smerdou, C., Martisova, E., Arozarena, I., Wellbrock, C., Llopiz, D., Ruiz, M., Sarobe, P., Breckpot, K., Kochan, G., & Escors, D.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 20
- Issue
- 8
- Pages
- 1818-1829
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2746892915
- Cited by
- 312
- References
- 32
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- gold
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