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 CD45+ 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 tumour chemotherapy.
Indrová
Marie
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, v. v. i., 142 20 Prague 4, Czech Republic. indrova@img.cas.cz
Bieblová
Jana
J
Rossowska
Joana
J
Kuropka
Piotr
P
Pajtasz-Piasecka
Elzbieta
E
Bubeník
Jan
J
Reinis
Milan
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D015316:Genetic Therapy; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D018664:Interleukin-12 / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy / Q000821:virology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; C097983:chlorobromofosfamide; D018664:Interleukin-12; D007069:Ifosfamide