title: Enhanced antitumor effect of combining chemotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes in mice with EBV-related non-Hodgkin's lymphoma.
abstract: Epstein-Barr virus (EBV)-related non-Hodgkin's lymphoma (NHL) represents a major problem in hematological clinical studies due to its drug tolerance and refractoriness. EBV infection is a key factor driving the process of tumor growth. Immune therapy is an important biotherapeutic method of treating cancer, which is attracting increasing attention. We hypothesized that combining conventional chemotherapy with immune therapy in the treatment of EBV-related NHL may achieve better outcomes. First, we successfully cloned large numbers of EBV-specific T cells by immune stimulationex vivo. Subsequently, the combined therapy was applied in a murine model of human EBV-related NHL. As expected, combined therapy inhibited tumor growth more effectively compared with monotherapy. In addition, we continuously tested the tumor-associated immune microenvironment and observed that the numbers of tumor-infiltrating cytotoxic T lymphocytes (CTLs) and macrophages were elevated following combined therapy. These effects suggest that EBV-specific CTLs may indirectly promote an innate immune reaction in lymphoma by activating tumor-infiltrating macrophage proliferation. Our findings may provide a guide for the prospective treatment of EBV-related NHL.
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Yi-Lan
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Fang-Yi
authors.initials: FY
authors.lastname: Fan
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Fu
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Ye-Cheng
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Translational Medicine, Experimental Medical Research Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Guo-Shun
authors.initials: GS
authors.lastname: Li
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Si-Han
authors.initials: SH
authors.lastname: Lai
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Miao
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Shuai
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Guang-Cui
authors.initials: GC
authors.lastname: He
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Y I
authors.initials: YI
authors.lastname: Wang
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Hao-Ping
authors.initials: HP
authors.lastname: Sun
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Hematology, Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Y I
authors.initials: YI
authors.lastname: Su
keywords: Epstein-Barr virus; chemotherapy; cytotoxic T cell; immunotherapy; lymphoma