I don't mean to be argumentative, however, I am rather confused by your response.
Firstly, according to the JTM article, it appears that the methylated group is doing far better in terms of delta and percentage survival as compared to unmethylated. And according to the graphic display, M+ is composed of proneural. If there is methylated MES, it is not mention and probably insignificant.
In prior studies and statements, LL was highly encouraged by results re MES. This is a very large molecular sub group and could consist of nearly 50% of ndGBM according to some studies. In other words, this group appears to be rather prevalent and therefore one would expect to find a significant percentage in middle of the road as you call it.
In discussing the effect of the vaccine on MES, there was no mention of methylated status. Rather, LL pointed out that this significant subgroup was much more immunogenic than say proneural. LL mentioned that in the case of MES, there is a higher level of killer T cells to begin with and further, there is a more reduced immunosuppressive tumor micro environment. The combination of a higher level of T cells synergistically combined with a lesser immunosuppressive environment allowed for more time for multiplied T cells to infiltrate the tumor. What was also exciting was that with this significant sub group, CI may not be required and DC VAX as a sole adjuvant to SOC(reducing tumour burden)would be sufficient. I frankly don't see the excitement if the vaccine is highly effective in a very small methylated subset of MES. The excitement, rather, was because the vaccine appeared to do so well in a broad subgroup that was highly aggressive and deadly. It also appears that M+ MOA works through a different pathway involving the inhibition of repair mechanisms on cancer cells this constraining proliferation.
At least, that is how I understand it and accordingly this could well be the basis of my confusion. If my understanding is otherwise correct, this would be extremely good news in that the vaccine works well in at least over 50% of ndGBM both in M+(Proneural) and M-(where MES is a major component along with
Classical). JMHO.
