title: Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice.
abstract: New strategies that stimulate cell-mediated immunity (CMI) against tumors and inhibit regulatory T cells are needed to improve the outcome of cancer immunotherapy. The aim of this study was to enhance the anti-tumor immunity of gp96 vaccine through naloxone administration. Therefore, we used BALB/c mouse model of fibrosarcoma tumor and analyzed the tumor size, splenocyte proliferation, spleen and tumor-infiltrated lymphocytes. Tumor and spleen CD4+CD25+Foxp3+ regulatory T lymphocytes, cytotoxic activity of the splenocytes, IFN-gamma and IL-4 secretion were assessed to describe the anti-tumor immune response. Our findings showed that co-administration of gp96 and naloxone has resulted in a significant reduction in CD4+CD25+Foxp3+ regulatory T cells in the spleen. The results indicated that on days 27 and 32 the tumors in the gp96+Nal group grew significantly slower. Moreover, co-administration of gp96 and naloxone significantly increased the intra-tumor CD8+ T cells and cytotoxic activity. In addition the results indicated a significant increase in the proliferation of splenocytes and IFN-gamma production. Our results demonstrate that naloxone is an effective immunoadjuvant in cancer immunotherapy.
authors.affiliation: Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Agheel Tabar
authors.initials: AT
authors.lastname: Molla Hassan
authors.forename: Zuhair M
authors.initials: ZM
authors.lastname: Hassan
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Moazzeni
authors.forename: Ali
authors.initials: A
authors.lastname: Mostafaie
authors.forename: Shahram
authors.initials: S
authors.lastname: Shahabi
authors.forename: Massoumeh
authors.initials: M
authors.lastname: Ebtekar
authors.forename: Seyed Mahmoud
authors.initials: SM
authors.lastname: Hashemi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000302:isolation & purification; D015704:CD4 Antigens; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit; D015847:Interleukin-4 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D009368:Neoplasm Transplantation; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D047368:Tumor Burden
chemical_list: D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D009292:Narcotic Antagonists; C052646:sarcoma glycoprotein gp96 rejection antigens; D015847:Interleukin-4; D009270:Naloxone; D007371:Interferon-gamma