The pilot study of anti-tumor effects versus immunosuppression of Staphylococcal Enterotoxin C.
Superantigens tremendously activate T lymphocytes by recognizing the particular region on TCR Vbeta, by which cytotoxic T cells can be well armed to kill tumor cells. However, the obstacle exists in the fact that immunosuppression is induced adversely. Staphylococcal enterotoxins (SEs) are pyrogenic superantigens who invoke T lymphocytes cytotoxicity at a very low dosage where their endotoxic activity diminishes. Despite that the elaborate mechanisms are largely unknown, tumoricidal capacity of SEA and SEB has been well studied. In this study, we devoted our attention to evaluate Staphylococcal Enterotoxin C (SEC) regarding its tumoricidal activity versus immunosuppression. We proved with flow cytometry that SEC treatment on C57 mice resulted in a boost of the differentiation of T lymphocytes into CD4(+), CD8(+) subpopulations. In vitro, SEC causes increased IFNgamma release from human PBMC. Furthermore, in coculture SEC-treated human PBMC led to more death of cancer cell lines from a variety of origins. Systemic SEC treatment in mouse and rabbit models significantly decreases tumor growth. In tumor-bearing rabbits, tumor necrosis and strong infiltration of lymphocytes into tumor tissue were observed; the rabbits also benefit with less metastasic cancer cells in the lung. In the meantime, the induced cell immune responses, both T cell differentiation and PBMC IFNgamma release, declined as SEC concentration rose. Tumor growth data obtained from animal models are in accordance with the changes in immunity, in which tumor growth ceased to respond to high dosage SEC as it did to lower dosage. These observations on SEC investigation, particularly in aspect of dosage-related immunosuppression, are of significance to SEC therapeutic potential to cancer. Molecular mechanism underlying these findings warrants further intensive investigation.
Jie
Ke-Ge
KG
State Key Laboratory of Pathogen and Biosecurity, The Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.
Jiang
Hua
H
Sun
Lei
L
Wang
Hai-Rong
HR
Zheng
Yu-Ling
YL
Li
Yi
Y
Jiang
Yong-Qiang
YQ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D010865:Pilot Projects; D011817:Rabbits; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D004768:Enterotoxins; D007166:Immunosuppressive Agents; C034959:enterotoxin C, staphylococcal; D007371:Interferon-gamma