HPV 16-associated tumours: IL-12 can repair the absence of cytotoxic and proliferative responses of tumour infiltrating cells after chemotherapy

We have examined the effect of IL-12-producing cellular vaccines on the cytotoxicity and proliferative potential of CD45(+) tumour-infiltrating cells (TIL) in mice carrying syngeneic TC-1 and TC-1/A9 HPV 16-associated tumours after chemotherapy with CBM-4A ifosfamide derivative. The chemotherapy resulted in the decrease of the CD4(+) and CD8(+) TIL, increase of the Gr-1(+)/CD11b(+) TIL, no changes in the infiltration with CD4(+)/CD25(+) Treg TIL, and decrease of the cytolytic and proliferative potential of the CD45(+) TIL. Subsequent immunotherapy with the IL-12-producing, genetically modified TC-1 (TC-1-IL-12) cells increased tumour infiltration with CD8(+) and CD4(+) cells, decreased the Gr-1(+)/CD11b(+) cells, and increased the cytolytic and proliferative potential of the CD41(+) TIL. Taken together, these findings suggest that peritumoral administration of the IL-12-producing cellular vaccine can restore the cytolytic potential and inhibit immunosuppressive TIL-dependent mechanisms in the individuals bearing HPV 16-associated tumours, and explain our previously described tumour-inhibitory effects Of the vaccine in mice with minimal residual disease after the turnout chemotherapy.