Publicaciones científicas

PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity

22-ago-2017 | Revista: Cell Reports

Maria Gato-Cañas  1 , Miren Zuazo  1 , Hugo Arasanz  2 , Maria Ibañez-Vea  1 , Laura Lorenzo  1 , Gonzalo Fernandez-Hinojal  2 , Ruth Vera  3 , Cristian Smerdou  4 , Eva Martisova  4 , Imanol Arozarena  1 , Claudia Wellbrock  5 , Diana Llopiz  4 , Marta Ruiz  4 , Pablo Sarobe  4 , Karine Breckpot  6 , Grazyna Kochan  7 , David Escors  8


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.

CITA DEL ARTÍCULO  Cell Rep. 2017 Aug 22;20(8):1818-1829. doi: 10.1016/j.celrep.2017.07.075

Nuestros autores

Dra. Diana Llópiz Khatchikian
Dra. Marta Ruiz Egozcue
Técnico de Investigación Grupo de Investigación en Péptidos