title: PD1 and PDL1 expression in primary central nervous system diffuse large B-cell lymphoma are frequent and expression of PD1 predicts poor survival.
abstract: Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare and aggressive type of diffuse large B-cell lymphoma (DLBCL) whit poorly understood pathogenesis. Finding biomarkers associated with patient survival may be important for understanding its physiopathology and to develop new therapeutic approaches. We investigated 32 PCNS-DLBCL from immunocompetent patients for BCL2, CMYC, LMO2, and P53 expression and for cytogenetic aberrations of BCL2, BCL6, and MYC genes, all known for their prognostic value in systemic DLBCL (s-DLBCL). We analyzed PD1 and PDL1 protein expression in both tumor infiltrating lymphocytes (TILs) and tumor cells. Finally, we searched for correlation between biological data and clinical course. The PCNS-DLBCL expressed BCL2, CMYC, LMO2, and P53 at similar frequency than s-DLBCL but without significant prognostic on survival. None cases harbored aberrations involving BCL2 and MYC gene whereas BCL6 abnormalities were present in 20.7% of cases but without value on survival. Expression of PD1 in TILs and PDL1 in tumor cells was observed at higher rates than in s-DLBCL (58% and 37%, respectively). The PD1 expression in TILs correlated with PDL1 expression in tumor cells (P = .001). Presence of PD1 positive TILs was associated with poorer overall survival (P = .011). Patients with PDL1 overexpression tended to better response to chemotherapy (P = .23). In conclusion PCNS-DLBCL pathogenesis differs from s-DLBCL without prognostic value of the phenotypic and cytogenetic parameters known for their pejorative impact in the latter. The PD1/PDL1 pathway plays a strong role in PCNS-DLBCL and represents an attractive target for this aggressive lymphoma.
authors.affiliation: Département de Biopathologie, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Four
authors.affiliation: Département d' Hématologie biologique, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.|Faculté de Médecine, Université Montpellier 1, Montpellier, France.
authors.forename: Valère
authors.initials: V
authors.lastname: Cacheux
authors.affiliation: Département de Biopathologie, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Tempier
authors.affiliation: Département d' Hématologie biologique, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.
authors.forename: Dolorès
authors.initials: D
authors.lastname: Platero
authors.affiliation: Département d' Oncologie Médicale, Institut du Cancer de Montpellier, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fabbro
authors.affiliation: Département d' Information Médicale, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Marin
authors.affiliation: Département de Biopathologie, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leventoux
authors.affiliation: Département de Biopathologie, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.|Faculté de Médecine, Université Montpellier 1, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Rigau
authors.affiliation: Département de Biopathologie, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.|Faculté de Médecine, Université Montpellier 1, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Costes-Martineau
authors.affiliation: Département de Biopathologie, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France.|Faculté de Médecine, Université Montpellier 1, Montpellier, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Szablewski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD1; PDL1; central nervous system; lymphoma