Naloxone can improve the anti-tumor immunity by reducing the CD4+CD25+Foxp3+ regulatory T cells in BALB/c mice.
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.
Molla Hassan
Agheel Tabar
AT
Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Hassan
Zuhair M
ZM
Moazzeni
Seyed Mohammad
SM
Mostafaie
Ali
A
Shahabi
Shahram
S
Ebtekar
Massoumeh
M
Hashemi
Seyed Mahmoud
SM
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
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