6533b830fe1ef96bd1297b50

RESEARCH PRODUCT

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

Giovanni ArpaGabriella NesiCatherine KlersyCarolina CiacciAntonietta D'erricoAnna D'odoricoMarco PaulliGino Roberto CorazzaFausto SessaValeria BarresiVittorio PerfettiFederica GrilloVincenzo CanzonieriRenato CannizzaroRoberto FioccaStefano FerreroLuca Reggiani BonettiDeborah MalviGiovanni LatellaPaolo PedrazzoliAntonio CalabròRoberto De GiorgioAlessandra ViglioFernando RizzelloFlavio CaprioliRoberto CaronnaDaniela FurlanAntonino Giulio GiannoneMarco SilanoMaurizio VecchiMichele MartinoFrancesco TonelliLaura CantoroAntonio Di SabatinoMaria D'armientoEnrico SolciaPaolo GiuffridaGianluca M. SampietroAda Maria FlorenaGiovanni MonteleoneLivia BianconeClaudia MescoliG. SolinaAndrea PietrabissaUmberto VoltaRenata D'incàOmbretta LuinettiVincenzo VillanacciLuca ElliMassimo RuggeMaria Cristina MacciomeiPaolo FocianiMarco AstegianoRachele CiccocioppoFabiana ZingoneClaudio PapiGiacomo CaioG. SandriBarbara OreggiaAlessandro VanoliAroldo RizzoElena BilettaAugusto OrlandiGilberto PoggioliAntonio CiardiMarco Vincenzo LentiPaolo UsaiErica QuaquariniDonatella SantiniSandro Ardizzone

subject

0301 basic medicineMalePD-L1 - small bowel adenocarcinoma - tumor-infiltrating lymphocytes - microsatellite instabilityPathologyBLOCKADEColorectal cancerLymphocyteSmall bowel adenocarcinomaGastroenterologyB7-H1 AntigenSettore MED/120302 clinical medicineCrohn DiseaseIntestine Smallsmall bowel adenocarcinomaSmall bowel adenocarcinomasMEDULLARY CARCINOMA; MORPHOLOGY; EXPRESSION; BLOCKADE; CANCERbiologymicrosatelliteinstabilityMiddle AgedCANCERmedicine.anatomical_structureMedullary carcinomatumor infiltrating lymphocytes030220 oncology & carcinogenesistumor-infiltrating lymphocytesAdenocarcinomaFemaleMicrosatellite InstabilityPD-L1Adultmedicine.medical_specialtysmall bowel adenocarcinoma tumor-infiltrating lymphocytes microsatelliteinstabilitySettore MED/08 - Anatomia PatologicaAdenocarcinomaMEDULLARY CARCINOMAPD-L1 small bowel adenocarcinomaNOPathology and Forensic Medicine03 medical and health sciencesLymphocytes Tumor-InfiltratingInternal medicinePD-L1expressionIntestinal NeoplasmsBiomarkers TumormedicineHumansPD-L1; small bowel adenocarcinoma; tumor infiltrating lymphocytesPD-L1 in small bowel adenocarcinoma MSI-HSmall bowel adenocarcinoma expression microsatellite instability biomarkersAgedRetrospective Studiesbusiness.industryTumor-infiltrating lymphocytesbiomarkersCancerCorrectionMicrosatellite instabilitymedicine.diseaseCeliac Disease030104 developmental biologybiology.proteinEtiologyMORPHOLOGYbusiness

description

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.

yearjournalcountryeditionlanguage
2020-01-01
10.1038/s41379-020-0497-0http://hdl.handle.net/11573/1457587