Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy.
- Author:
Jia HE
1
;
Xiao-Feng TANG
;
Qiu-Yan CHEN
;
Hai-Qiang MAI
;
Zhou-Feng HUANG
;
Jiang LI
;
Yi-Xin ZENG
Author Information
- Publication Type:Journal Article
- MeSH: Biopsy; CD3 Complex; analysis; CD4 Antigens; analysis; CD8 Antigens; analysis; Cells, Cultured; Herpesvirus 4, Human; immunology; Humans; Immunotherapy, Adoptive; Interferon-gamma; metabolism; Interleukin-10; metabolism; Interleukin-2; pharmacology; Interleukin-4; metabolism; Lymphocytes, Tumor-Infiltrating; immunology; virology; Monocytes; pathology; Muromonab-CD3; pharmacology; Nasopharyngeal Neoplasms; immunology; pathology; therapy; virology; Receptors, IgG; analysis; T-Lymphocytes, Cytotoxic; immunology; virology; Tumor Necrosis Factor-alpha; metabolism
- From:Chinese Journal of Cancer 2012;31(6):287-294
- CountryChina
- Language:English
- 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.
