HPV 16-associated tumours: IL-12 can repair the absence of cytotoxic and proliferative responses of tumour infiltrating cells after chemotherapy
Marie Indrová , Jana Bieblová , Joana Rossowska , Piotr Kuropka , Elzbieta Pajtasz-Piasecka , Jan Bubeník , Milan Reinis
AbstractWe 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.
|Journal series||International Journal of Oncology, ISSN 1019-6439, e-ISSN 1791-2423, (A 25 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||Cytotoxicity; HPV16; Tumour-infiltrating cells; Vaccines|
|License||Journal (articles only); published final; ; with publication|
|Publication indicators||= 17; = 16; : 2009 = 0.761; : 2009 = 2.447 (2) - 2009=2.324 (5)|
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