RT Journal Article T1 Analysis of expression of the PD-1/PD-L1 immune checkpoint system and its prognostic impact in gastroenteropancreatic neuroendocrine tumors A1 Sampedro Núñez, Miguel A1 Serrano Somavilla, Ana A1 Adrados, Magdalena A1 Cameselle Teijeiro, José Manuel A1 Blanco Carrera, Concepción A1 Cabezas Agrícola, José Manuel A1 Martínez Hernández, Rebeca A1 Martín Pérez, Elena A1 Muñoz de Nova, José Luis A1 Díaz, José Ángel A1 García Centeno, Rogelio A1 Caneiro Gómez, Javier A1 Abdulkader Nallib, Ihab A1 González Amaro, Roberto A1 Marazuela, Mónica AB The immune checkpoint based therapy targeting the programmed death-1 (PD-1) receptor and its PD-L1 ligand has recently been approved for the therapy of different malignant conditions, but not yet for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this context, we evaluated the expression of PD-1 and PD-L1 in GEP-NETs and its potential correlations with clinical outcomes. Expression of PD-1/PD-L1 was analyzed by immunohistochemistry in 116 GEP-NETs and 48 samples of peritumoral tissue. In addition, the expression of these molecules was assessed by flow cytometry in peripheral blood mononuclear cells (PBMC) from patients with GEP-NETs (n = 32) and healthy controls (n = 32) and in intratumoral mononuclear cells (TMCs) (n = 3). Expression of PD-L1 and PD-1 was detected by immunohistochemistry in 6% and 1% of tumor tissue samples, respectively, and in 8% of peritumoral tissue samples, for both markers. We also observed that PD-1 expression by TMCs was associated with metastatic disease at diagnosis, and the levels of circulating PD-1+ PBMCs were associated with progressive disease upon follow-ups. In addition, circulating PD-1+ PBMCs were significantly correlated with PD-L1 expression by tumor cells. Our data suggest that PD-1/PD-L1 is expressed in 1 to 8% of GEP-NETs, and that this feature is significantly associated with disease evolution (p < 0.01). PB Nature Publishing Group YR 2018 FD 2018 LK http://hdl.handle.net/10347/22584 UL http://hdl.handle.net/10347/22584 LA eng NO Sampedro-Núñez, M., Serrano-Somavilla, A., Adrados, M. et al. Analysis of expression of the PD-1/PD-L1 immune checkpoint system and its prognostic impact in gastroenteropancreatic neuroendocrine tumors. Sci Rep 8, 17812 (2018). https://doi.org/10.1038/s41598-018-36129-1 NO This work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041 and PI16-02091 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), GETNE G1707 (funded by Grupo Español de Tumores Neuroendocrinos y Endocrinos) to M.M. Proyectos de Investigación en Salud (FIS) PI15/01501-FEDER (funded by Instituto de Salud Carlos III) to J.C.T. DS Minerva RD 29 abr 2026