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PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.
Modern Pathology ( IF 6.365 ) Pub Date : 2020-02-17 , DOI: 10.1038/s41379-020-0497-0
Paolo Giuffrida,Giovanni Arpa,Federica Grillo,Catherine Klersy,Gianluca Sampietro,Sandro Ardizzone,Paolo Fociani,Roberto Fiocca,Giovanni Latella,Fausto Sessa,Antonietta D'Errico,Deborah Malvi,Claudia Mescoli,Massimo Rugge,Gabriella Nesi,Stefano Ferrero,Daniela Furlan,Gilberto Poggioli,Fernando Rizzello,Maria C Macciomei,Donatella Santini,Umberto Volta,Roberto De Giorgio,Giacomo Caio,Antonio Calabrò,Carolina Ciacci,Maria D'Armiento,Aroldo Rizzo,Gaspare Solina,Michele Martino,Francesco Tonelli,Vincenzo Villanacci,Renato Cannizzaro,Vincenzo Canzonieri,Ada M Florena,Livia Biancone,Giovanni Monteleone,Roberto Caronna,Antonio Ciardi,Luca Elli,Flavio Caprioli,Maurizio Vecchi,Renata D'Incà,Fabiana Zingone,Anna D'Odorico,Marco Vincenzo Lenti,Barbara Oreggia,Luca Reggiani Bonetti,Marco Astegiano,Elena Biletta,Laura Cantoro,Antonino G Giannone,Augusto Orlandi,Claudio Papi,Vittorio Perfetti,Erica Quaquarini,Giancarlo Sandri,Marco Silano,Paolo Usai,Valeria Barresi,Rachele Ciccocioppo,Ombretta Luinetti,Paolo Pedrazzoli,Andrea Pietrabissa,Alessandra Viglio,Marco Paulli,Gino R Corazza,Enrico Solcia,Alessandro Vanoli,Antonio Di Sabatino

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
更新日期:2020-02-18

 

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