title: PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.
abstract: Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1) antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB)-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.
authors.affiliation: Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Quan
authors.affiliation: Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Aichun
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Xiuchen
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D016207:Cytokines; D061026:Programmed Cell Death 1 Receptor