Maintenance of CD8 effector T cells by CD4 helper T cells eradicates growing tumors and promotes long-term tumor immunity.
Human papillomavirus, particularly type 16 (HPV-16), is present in more than 99% of cervical cancers, and oncogenic HPV infection is one of the most important etiologies. It is now clear that CD4(+) T cells play an important role in controlling HPV-associated lesions because immunocompromised patients have a higher frequency of HPV-associated lesions. In the current study, we characterized the significance of CD4(+) T cells in the generation of E7-specific CD8(+) T cell immune responses in mice vaccinated with SINrep5-E7/HSP70 and boosted with vac-E7/HSP70. In addition, we characterized the contribution of CD4(+) T cells to the long-term antitumor effects. We found that vaccination with CD4 depletion significantly reduced the number of E7-specific CD8(+) T cells in mice. Furthermore, CD4(+) T cells are important for the long-term anti-tumor effects generated by vaccination with SINrep5-E7/HSP70 and booster with vac-E7/HSP70. Thus, CD4 T cells clearly have an important role in successful tumor immunity and maintenance of long-term tumor antigen-specific memory responses in vaccinated mice with established tumors.
Lin
Cheng-Tao
CT
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5, Fu-Shin Street, Kweishan, Taoyuan, Taiwan. 51424@cgmh.org.tw
Chang
Ting-Chang
TC
Shaw
Sheng-Wen
SW
Cheng
Po-Jen
PJ
Huang
Ching-Tai
CT
Chao
Angel
A
Soong
Yung-Kuei
YK
Lai
Chyong-Huey
CH
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000254:growth & development*; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology; D012845:Sindbis Virus / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16