Multiple molecular and cellular changes associated with tumour stasis and regression during IL-12 therapy of a murine breast cancer model
✍ Scribed by Sergio Dias; Hilary Thomas; Frances Balkwill
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 130 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
IL-12 treatment of a murine transplantable breast carcinoma (HTH-K) led to tumour regression and cure which was related to the duration of treatment. We studied the sequential molecular and phenotypic changes in IL-12-treated tumours. IFN-␥ mRNA was detected 8 hr after the first treatment. mRNA expression for the IFN-␥-inducible genes  2 -microglobulin and indoleamine dioxygenase (IDO) was induced subsequently, together with the chemokine IP-10. IL-12-treated tumours had an abundant cellular infiltrate, consisting mainly of CD8 ؉ T cells. mRNA for granzyme B and perforin also could be detected, suggesting that those cells were activated. After 7 days of daily therapy, tumours in IL-12-treated mice had a significant reduction in vasculature. Finally, the number of apoptotic tumour cells increased throughout IL-12 treatment. We compared the anti-tumour effects of IL-12 to those induced by IFN-␥ therapy, which caused initial tumour stasis but subsequent tumour progression. IFN-␥ induced  2 -microglobulin and IDO over a 7-day period, but IP-10 was induced only transiently. IFN-␥ caused a lesser cellular infiltrate, a minor anti-angiogenic effect and a transient apoptotic effect. The success of IL-12 may be due to its ability to produce a distinct sequence of molecular and phenotypic changes in tumours, leading to an anti-tumour immune response, toxicity against tumour cells and an antiangiogenic effect. Other cytokines, such as IFN-␥, induce some, but not all, of these actions. Comparison of IL-12 and IFN-␥ suggests that sustained induction of IP-10 and activation of a resulting cellular infiltrate may be key changes in regressing tumours.