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.