I have been puzzled by whether there is some correlation between Methylated/Unmethylated(M+/M-) MGMT and Mesenchymal. I don't know and the research I have done has not indicated a clear correlation.
In the case of M+, life expectancy and SOC typically is long lasting. The 35 patient study written in 2015 cites M+ SOC at about an mOS of 29 months. If I recall correctly, the pub cited an mOS of about 22-23 months. M-, on the other hand, is more aggressive and an mOS of about 12.7 months was cited. Mesenchymal is also very aggressive and highly heterogeneous as well as mutational. Thus, mesenchymal has some characteristics of M+ but the big difference is that mesenchymal is very aggressive like M-. Mesenchymal is also characterised by mutations of NF-1(among other deletions/transcription factors). Apparently, mesenchymal is more immunogenic meaning that the tumour micro-environment is less suppressive allowing more time for increased T cells, indeed the full arsenal of the immune system, to infiltrate the tumour and attack it before the immune system turns off. That is why, it is hypothesised, that DC VAX L can work very effectively without checkpoint inhibitors because of the immunogenicity of the mesenchymal strain.
M+ is as stated above much less aggressive and more like pro-neural in that particular regard. Methylation reduces expression of MGMT and thus the cellular repair mechanism. M+, according to the publication with an N=131, was 39.6% of the entire clinical population and about 42% of the counted M+/M-population of 293 where M- N=162 taking into account the 38 patients that were not identified as either M+ or M-(or other). So a significantly large proportion of patients, of the M+ variety, appear to be responding very well to the vaccine, at least close to 40% at a minimum. It could, indeed, be a higher proportion if, in addition, mesenchymal is not fully inclusive in M+ but is rather net additive as a part of M- where the vaccine appears to have some effect. So, it may be quite possible that DC VAX L is quite effective on perhaps 50% of the clinical population. However, this may depend somewhat upon mesenchymal/M+M- correlations. JMHO.
