OK...here we go, will do this in small bits since I know you are not familiar with this science
The data represented in Fig 2 is what originally caught my eye in earlier abst presentations, which we now know is not associated with changes in immune cell sub-sets (Fig 4). Data in fig 5 confirms the IFN response (panel A) but now we see that 50% of the PV-10 induced in vitro cell killing effect is attributed to a saline effect (Fig 5b, compare B16 vs PBS or PV-10). Never mind that I speculated there would be a saline effect years ago.
Because this effect is not attributed to PV-10, is not associated with elevated INF, but does account for 50% of the biologic response we know that there may be two systems at work in this mouse model (maybe more, certainly not less than two), a general effect of lesion injection, and an additional effect of RB. What we dont know is which contributes more to the biologic response.
The elegant next step would have been to treat tumor bearing mice IL with PV-10 or saline, isolate cells from the spleen of each group, and independently transfer those spleen cells to a second set of tumor bearing mice to test the transferability of the apparent saline and apparent PV-10 effect.
Unfortunately, in Fig 6, these investigators only followed up with the splenocytes from PV-10 treated primary animals (despite seeing the data for the saline group, they choose to not look at them further). When secondary tumor bearing animals were treated with T cells isolated from PV-10 treated primary animals we see that these T cells blunted, but did not eliminate, tumor growth in these secondary animals.
We still do not know if this effect could have been replicated by T cells from IL saline treated primary animals, and now have to conclude that INF may not be an ideal marker to use in monitoring this effect as it missed over 50% of the biologic signal (Fig 5b).
This is why I prefer seeing published data, you can get so much more out of the information presented. It is true that animals treated with PV-10 results in an effect that can be transplanted to secondary animals, but we now have no idea if they transferred the saline effect or an RB effect...which is probably why this was not published in a main stream oncology or immunology journal. |