title: Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy.
abstract: Establishing Epstein-Barr virus(EBV)-specific cytolytic T lymphocytes(EBV-CTLs) from peripheral blood mononuclear cells(PBMCs) for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma(NPC). In the current study, we performed ex vivo expansion of tumor-infiltrating lymphocytes(TILs) obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody(OKT3), recombinant human interleukin(IL)-2, and irradiated PBMCs from healthy donors to initiate the growth of TILs. Young TIL cultures comprised of more than 90% of CD3+ T cells, a variable percentage of CD3+CD8+ and CD3+CD4+ T cells, and less than 10% of CD3-CD16+ natural killer cells, a similar phenotype of EBV-CTL cultures from PBMCs. Interestingly, TIL cultures secreted high levels of the Th1 cytokines, interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α), and low levels of the Th2 cytokines, IL-4 and IL-10. Moreover, young TILs could recognize autologous EBV-transformed B lymphoblast cell lines, but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells. Taken together, these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tang
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.forename: Zhou-Feng
authors.initials: ZF
authors.lastname: Huang
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
mesh_terms: D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000821:virology; D009000:Monocytes / Q000473:pathology; D016853:Muromonab-CD3 / Q000494:pharmacology*; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D017452:Receptors, IgG / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D016853:Muromonab-CD3; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma