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

P. Giuffrida, G. Arpa, F. Grillo, C. Klersy, G. Sampietro, S. Ardizzone, P. Fociani, R. Fiocca, G. Latella, F. Sessa, A. D’Errico, D. Malvi, C. Mescoli, M. Rugge, G. Nesi, S. Ferrero, D. Furlan, G. Poggioli, F. Rizzello, M.C. MacciomeiD. Santini, U. Volta, R. De Giorgio, G. Caio, A. Calabrò, C. Ciacci, M. D’Armiento, A. Rizzo, G. Solina, M. Martino, F. Tonelli, V. Villanacci, R. Cannizzaro, V. Canzonieri, A.M. Florena, L. Biancone, G. Monteleone, R. Caronna, A. Ciardi, L. Elli, F. Caprioli, M. Vecchi, R. D’Incà, F. Zingone, A. D’Odorico, M.V. Lenti, B. Oreggia, L. Reggiani Bonetti, M. Astegiano, E. Biletta, L. Cantoro, A.G. Giannone, A. Orlandi, C. Papi, V. Perfetti, E. Quaquarini, G. Sandri, M. Silano, P. Usai, V. Barresi, R. Ciccocioppo, O. Luinetti, P. Pedrazzoli, A. Pietrabissa, A. Viglio, M. Paulli, G.R. Corazza, E. Solcia, A. Vanoli, A. Di Sabatino

Research output: Contribution to journalArticlepeer-review


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.

Original languageItalian
Pages (from-to)1398-1409
Number of pages12
JournalModern Pathology
Issue number7
Publication statusPublished - 2020

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