title: Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients.
abstract: Plasmablastic lymphoma is a rare and aggressive diffuse large B-cell lymphoma commonly associated with Epstein-Barr virus co-infection that most often occurs in the context of human immunodeficiency virus infection. Therefore, its immune escape strategy may involve the upregulation of immune-checkpoint proteins allowing the tumor immune evasion. However, the expression of these molecules was poorly studied in this lymphoma. We have investigated 82 plasmablastic lymphoma cases of whom half were Epstein-Barr virus positive. Although they harbored similar pathological features, Epstein-Barr virus positive plasmablastic lymphomas showed a significant increase in MYC gene rearrangement and had a better 2-year event-free survival than Epstein-Barr virus negative cases (P=0.049). Immunostains for programmed cell death-1, programmed cell death-ligand 1, indole 2,3-dioxygenase and dendritic cell specific C-type lectin showed a high or moderate expression by the microenvironment cells in 60%-72% of cases, whereas CD163 was expressed in almost all cases. Tumor cells also expressed programmed cell death-1 and its ligand in 22.5% and 5% of cases, respectively. Both Epstein-Barr virus positive and negative plasmablastic lymphomas exhibited a high immune-checkpoint score showing that it involves several pathways of immune escape. However, Epstein-Barr virus positive lymphomas exhibited a higher expression of programmed cell death-1 and its ligand in both malignant cells and microenvironment as compared to Epstein-Barr virus negative cases. In conclusion, plasmablastic lymphoma expresses immune-checkpoint proteins through both malignant cells and the tumor microenvironment. The expression of programmed cell death-1 and its ligand constitutes a strong rationale for testing monoclonal antibodies in this often chemoresistant disease.
authors.affiliation: Département de Pathologie, Institut Universitaire du Cancer-Oncopole, Toulouse, France INSERM, U.1037, Centre de Recherche en Cancérologie de Toulouse-Purpan, Toulouse, France laurent.c@chu-toulouse.fr.
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.affiliation: Département de Pathologie, AP-HP, Hôpital Saint-Antoine, Paris, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Fabiani
authors.affiliation: Institute for Cancer Genetics, Columbia University, New York, NY, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Do
authors.affiliation: Service d'Hematologie, Hôpital Gui de Chauliac-Saint Eloi, Montpellier, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Tchernonog
authors.affiliation: Service d'Hematologie, Hôpital Gui de Chauliac-Saint Eloi, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
authors.affiliation: Département de Pathologie, Institut Universitaire du Cancer-Oncopole, Toulouse, France INSERM, U.1037, Centre de Recherche en Cancérologie de Toulouse-Purpan, Toulouse, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Gravelle
authors.affiliation: Département de Pathologie, Institut Universitaire du Cancer-Oncopole, Toulouse, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Amara
authors.affiliation: Service d'Hématologie, AP-HP, Hôpital Saint-Antoine, Paris, France Centre de Référence des Microangiopathies Thrombotiques, AP-HP, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Malot
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Maryknoll Mawanay
authors.initials: MM
authors.lastname: Palisoc
authors.affiliation: Département de Pathologie, AP-HP, Groupe Hospitalier Henri Mondor - Albert henevier, Créteil, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Copie-Bergman
authors.affiliation: Département de Pathologie, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Alexandra Traverse
authors.initials: AT
authors.lastname: Glehen
authors.affiliation: Département de Pathologie, Centre Hospitalier Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.affiliation: Département de Pathologie, Institut Universitaire du Cancer-Oncopole, Toulouse, France INSERM, U.1037, Centre de Recherche en Cancérologie de Toulouse-Purpan, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Brousset
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.affiliation: Service d'Hématologie, AP-HP, Hôpital Saint-Antoine, Paris, France Centre de Référence des Microangiopathies Thrombotiques, AP-HP, Paris, France UPMC, Université Paris VI, France Inserm U1170, Institut Gustave Roussy, Villejuif, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001706:Biopsy; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D056747:Immunomodulation / Q000235:genetics*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069293:Plasmablastic Lymphoma / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor