Abstract
Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD)/lymphomas in nonimmunosuppressed patients represent a unique entity and have been proposed to be related to immune senescence. Engagement of programmed cell death 1 (PD1) by its ligand programmed death ligand 1 (PDL1) inhibits T-cell activation, and leads to T-cell exhaustion. In clinical trials, therapeutic antibodies that block the PD1-PDL1 axis have shown promising therapeutic activity in certain types of lymphomas. Although PD1/PDL1 has been extensively studied in variety of lymphomas, there are few reports characterizing their expression in EBV-positive LPD. As these group of patients are presumed to be associated with immunosenescence/immune dysregulation, we hypothesize that the immune checkpoint pathway might be relevant in this entity. We explored the expression of PD1, PDL1 and its clinicopathologic association in 6 patients with a total of 8 independent specimens of EBV-positive LPD/lymphomas. We also applied proximity assay, a novel technique, which can identify intermolecular interaction, to evaluate physical interaction or in situ engagement of PD1 and PDL1. We found that the malignant cells in the EBV-positive LPDs express PDL1. PD1-positive ...Continue Reading
References
Oct 4, 2000·The Journal of Experimental Medicine·G J FreemanT Honjo
Apr 17, 2007·Current Opinion in Immunology·Mary E KeirArlene H Sharpe
Jun 15, 2007·Molecular & Cellular Proteomics : MCP·Malin JarviusOla Söderberg
Sep 6, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takashi OyamaShigeo Nakamura
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
May 16, 2008·Human Pathology·Luc XerriDaniel Olive
May 24, 2008·Clinical Chemistry·Sigrun M GustafsdottirUlf Landegren
May 27, 2008·Nature Reviews. Immunology·Weiping Zou, Lieping Chen
Mar 10, 2011·Blood·Stefan D DojcinovElaine S Jaffe
Mar 21, 2013·British Journal of Cancer·S A Quezada, K S Peggs
May 16, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Benjamin J ChenScott J Rodig
Oct 16, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philippe ArmandLeo I Gordon
Dec 18, 2013·The Lancet Oncology·Jason R WestinSattva S Neelapu
Sep 28, 2014·Blood Reviews·Locke J Bryan, Leo I Gordon
Nov 28, 2014·Nature·Paul C TumehAntoni Ribas
Dec 9, 2014·The New England Journal of Medicine·Stephen M AnsellPhilippe Armand
May 20, 2015·Current Oncology Reports·Loretta J Nastoupil, Sattva S Neelapu
Aug 5, 2015·Blood·Junichi KiyasuKoichi Ohshima
Oct 2, 2015·Histopathology·Dohee KwonYoon Kyung Jeon
Mar 17, 2016·Blood·Steven H SwerdlowElaine S Jaffe
May 14, 2016·Haematologica·Camille LaurentPaul Coppo
Jun 30, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philippe ArmandCraig H Moskowitz
Oct 4, 2016·Haematologica·Fabienne McClanahanJohn G Gribben
Apr 14, 2017·Oncotarget·Pauline GravelleCamille Laurent