Tumour susceptibility to innate and adaptive immunotherapy changes during tumour maturation.
Immunotherapy of tumours using T cells expanded in vitro has met with mixed clinical success suggesting that a greater understanding of tumour/T-cell interaction is required. We used a HPV16E7 oncoprotein-based mouse tumour model to study this further. In this study, we demonstrate that a HPV16E7 tumour passes through at least three stages of immune susceptibility over time. At the earliest time point, infusion of intravenous immune cells fails to control tumour growth although the same cells given subcutaneously at the tumour site are effective. In a second stage, the tumour becomes resistant to subcutaneous infusion of cells but is now susceptible to both adjuvant activated and HPV16E7-specific immune cells transferred intravenously. In the last phase, the tumour is susceptible to intravenous transfer of HPV16E7-specific cells, but not adjuvant-activated immune cells. The requirement for IFN-gamma and perforin also changes with each stage of tumour development. Our data suggest that effective adoptive T-cell therapy of tumour will need to be matched with the stage of tumour development.
Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, QLD 4102, Australia.
Trina J
TJ
Stewart
Germain J P
GJ
Fernando
Ian H
IH
Frazer
Graham R
GR
Leggatt
D000818:Animals; D002461:Cell Line, Transformed; D018450:Disease Progression; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D052899:Pore Forming Cytotoxic Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D054353:Perforin; D007371:Interferon-gamma