Local IFN-gamma therapy of HPV16-associated tumours.
We have examined whether peritumoral administration of IFN-gamma can inhibit growth of HPV16-associated, MHC class I- tumour MK16/1/IIIABC (MK16) transplanted in syngeneic mice. It has been found that peritumoral administration of recombinant IFN-gamma performed on days 0-11 after tumour challenge inhibited growth of MK16 s.c. tumour transplants. If the therapy with IFN-gamma was started when the tumours had already reached a palpable size, the IFN-gamma administration was without any effect. To investigate the antitumour effects of IFN-gamma in a clinically more relevant setting, surgical minimal residual tumour disease was utilized. Subcutaneously growing MK16 carcinomas, 8-12 mm in diameter, were removed and the operated mice were injected with IFN-gamma on days 3-14 after the operation at the site of surgery. Treatment with IFN-gamma resulted in a moderate, reproducible, but statistically insignificant inhibition of tumour recurrences. In the next experiments we have addressed the question whether the tumour-inhibitory effect of IFN-gamma was due to the upregulation of MHC class I molecule expression on MK16 tumour cells. IFN-gamma-treated and control mice were sacrificed, their tumours were explanted, and the expression of MHC class I molecules on the MK16 tumour cells was examined. As presumed, the MHC class I expression on the cells of IFN-gamma-treated tumours, as well as on their lung metastases, was upregulated. However, an unexpected moderate upregulation of the MHC class I expression was also observed on MK16 tumours from the control, exogenous IFN-gamma-uninjected mice. Cytofluorometric analysis of the in vivo transplanted MK16 tumours from both groups has excluded that the increased percentage of the MHC class I molecules on the tumour cell populations could be due to the infiltration of the tumours with MHC class I+ leukocytes, since no expression of MHC class II, CD11b, CD80/CD86, and CD11c molecules in the MK16 cell population was observed.
Mikysková
R
R
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Bieblová
J
J
Símová
J
J
Indrová
M
M
Jandlová
T
T
Vonka
V
V
Smahel
M
M
Bubeník
J
J
Mendoza
L
L
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000821:virology; D027383:Papillomaviridae / Q000187:drug effects; D030361:Papillomavirus Infections / Q000188:drug therapy*; D014412:Tumor Virus Infections / Q000188:drug therapy*
D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma