title: Prognostic value of PDL1 expression in pancreatic cancer.
abstract: Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples. Upregulation was not associated with clinicopathological features such as patients' age and sex, pathological type, tumor size, lymph node status, and grade, but was associated with shorter disease-free survival and overall survival in multivariate analyses. Analysis of correlations with biological parameters showed that PDL1 upregulation was associated with some degree of lymphocyte infiltration and signs of anti-tumor T-cell response, but to a lesser extent than what has been reported in breast cancer and GIST. PDL1-up pancreatic cancers displayed profiles of lymphocyte exhaustion, were more enriched in inhibitory molecules and pro-tumor populations (Tregs with upregulation of FOXP3 and IL10, myeloid-derived suppressor cells with upregulation of CD33 and S100A8/A9), and demonstrated a down-modulation of most MHC class I members (HLA-A/B/C, HLA-E/F/G) suggestive of a defect in antigen processing and presentation. In conclusion, our results suggest that PDL1 expression might refine the prediction of metastatic relapse in operated pancreatic cancer, and that PD1/PDL1 inhibitors might reactivate inhibited T-cells to increase the anti-tumor immune response in PDL1-upregulated tumors.
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France.|Département de Chirurgie Générale et Viscérale, AP-HM, Marseille, France.|Faculté de Médecine, Aix-Marseille Université, Marseille, France.
authors: David J
authors: DJ
authors: Birnbaum
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France.
authors: Pascal
authors: P
authors: Finetti
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France.
authors: Alexia
authors: A
authors: Lopresti
authors: Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.|Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France.
authors: Marine
authors: M
authors: Gilabert
authors: Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.|Département d'Anatomopathologie, Institut Paoli-Calmettes, Marseille, France.
authors: Flora
authors: F
authors: Poizat
authors: Faculté de Médecine, Aix-Marseille Université, Marseille, France.|Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.|Département d'Oncologie Chirurgicale, Institut Paoli-Calmettes, Marseille, France.
authors: Olivier
authors: O
authors: Turrini
authors: Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.|Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France.
authors: Jean-Luc
authors: JL
authors: Raoul
authors: Faculté de Médecine, Aix-Marseille Université, Marseille, France.|Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.|Département d'Oncologie Chirurgicale, Institut Paoli-Calmettes, Marseille, France.
authors: Jean-Robert
authors: JR
authors: Delpero
authors: Département de Chirurgie Générale et Viscérale, AP-HM, Marseille, France.
authors: Vincent
authors: V
authors: Moutardier
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France.|Faculté de Médecine, Aix-Marseille Université, Marseille, France.
authors: Daniel
authors: D
authors: Birnbaum
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France.|Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.
authors: Emilie
authors: E
authors: Mamessier
authors: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France.|Faculté de Médecine, Aix-Marseille Université, Marseille, France.|Equipe de Médecine Translationelle Hépato-Gastro-Entérologie, Institut Paoli-Calmettes, Marseille, France.|Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France.
authors: François
authors: F
authors: Bertucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D060890:B7-H1 Antigen / Q000235:genetics / Q000502:physiology*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: PDL1; expression; immune response; pancreatic cancer; survival