Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine.
Single administration of low dose cyclophosphamide (CTX) was previously reported to enhance the antitumor efficacy of immunotherapies. To investigate the possible mechanisms for this effect, we examined whether a single administration of low dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty milligrams per kilogram body weight dose of CTX was administrated intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models were established, DC vaccine generated from mouse bone marrow and pulsed with B16 or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment potentiated the antitumor effects of the DC vaccine, and increased the proportion of IFN-gamma secreting lymphocytes in spleens. Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX. Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Treg cells in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced immunopotentiation and provided a strategy of immunotherapy combining a low dose CTX with DC vaccine.
Liu
Ji-Yan
JY
State Key Laboratory of Oncology in South China and Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan, Guangdong, People's Republic of China.
Wu
Yang
Y
Zhang
Xiao-Shi
XS
Yang
Jin-Liang
JL
Li
Hong-Li
HL
Mao
Yong-Qiu
YQ
Wang
Yi
Y
Cheng
Xia
X
Li
Yong-Qiang
YQ
Xia
Jian-Chuan
JC
Masucci
Maria
M
Zeng
Yi-Xin
YX
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D015704:CD4 Antigens / Q000032:analysis; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D016233:Immunotherapy, Active / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008546:Melanoma, Experimental; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D018906:Antineoplastic Agents, Alkylating; D015704:CD4 Antigens; D019496:Cancer Vaccines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma; D003520:Cyclophosphamide