Oncotarget

Research Papers:

Prognostic value of PDL1 expression in pancreatic cancer

David J. Birnbaum, Pascal Finetti, Alexia Lopresti, Marine Gilabert, Flora Poizat, Olivier Turrini, Jean-Luc Raoul, Jean-Robert Delpero, Vincent Moutardier, Daniel Birnbaum, Emilie Mamessier and François Bertucci _

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Oncotarget. 2016; 7:71198-71210. https://doi.org/10.18632/oncotarget.11685

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Abstract

David J. Birnbaum1,2,3, Pascal Finetti1, Alexia Lopresti1, Marine Gilabert4,5, Flora Poizat4,7, Olivier Turrini3,4,6, Jean-Luc Raoul4,5, Jean-Robert Delpero3,4,6, Vincent Moutardier2, Daniel Birnbaum1,3, Emilie Mamessier1,4,* and François Bertucci1,3,4,5,*

1 Département d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Université Aix-Marseille, Marseille, France

2 Département de Chirurgie Générale et Viscérale, AP-HM, Marseille, France

3 Faculté de Médecine, Aix-Marseille Université, Marseille, France

4 Equipe de Médecine Translationelle Hépato-gastro-entérologie, Institut Paoli-Calmettes, Marseille, France

5 Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France

6 Département d’Oncologie Chirurgicale, Institut Paoli-Calmettes, Marseille, France

7 Département d’Anatomopathologie, Institut Paoli-Calmettes, Marseille, France

* These authors have equally contributed to this work

Correspondence to:

François Bertucci, email:

Keywords: expression, immune response, pancreatic cancer, PDL1, survival

Received: May 10, 2016 Accepted: August 24, 2016 Published: August 29, 2016

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.


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