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ADA MARIA FLORENA

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability

  • Autori: Giuffrida, Paolo; Arpa, Giovanni; Grillo, Federica; Klersy, Catherine; Sampietro, Gianluca; Ardizzone, Sandro; Fociani, Paolo; Fiocca, Roberto; Latella, Giovanni; Sessa, Fausto; D'Errico, Antonietta; Malvi, Deborah; Mescoli, Claudia; Rugge, Massimo; Nesi, Gabriella; Ferrero, Stefano; Furlan, Daniela; Poggioli, Gilberto; Rizzello, Fernando; Macciomei, Maria C; Santini, Donatella; Volta, Umberto; De Giorgio, Roberto; Caio, Giacomo; Calabrò, Antonio; Ciacci, Carolina; D'Armiento, Maria; Rizzo, Aroldo; Solina, Gaspare; Martino, Michele; Tonelli, Francesco; Villanacci, Vincenzo; Cannizzaro, Renato; Canzonieri, Vincenzo; Florena, Ada M; Biancone, Livia; Monteleone, Giovanni; Caronna, Roberto; Ciardi, Antonio; Elli, Luca; Caprioli, Flavio; Vecchi, Maurizio; D'Incà, Renata; Zingone, Fabiana; D'Odorico, Anna; Lenti, Marco Vincenzo; Oreggia, Barbara; Reggiani Bonetti, Luca; Astegiano, Marco; Biletta, Elena; Cantoro, Laura; Giannone, Antonino G; Orlandi, Augusto; Papi, Claudio; Perfetti, Vittorio; Quaquarini, Erica; Sandri, Giancarlo; Silano, Marco; Usai, Paolo; Barresi, Valeria; Ciccocioppo, Rachele; Luinetti, Ombretta; Pedrazzoli, Paolo; Pietrabissa, Andrea; Viglio, Alessandra; Paulli, Marco; Corazza, Gino R; Solcia, Enrico; Vanoli, Alessandro; Di Sabatino, Antonio
  • Anno di pubblicazione: 2020
  • Tipologia: Articolo in rivista
  • OA Link: http://hdl.handle.net/10447/510302

Abstract

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.