Came across this, which is an lengthy advertisement but well cited about how enzymatically modified rice bran (EMRB)/Arabinoxylan substantially increases the cytotoxicity of natural killer white cells.
http://www.lifeextension.com/magazine/2015/1/activate-your-natural-killer-cells/page-01
Here's the NCBI abstract:
https://www.ncbi.nlm.nih.gov/pubmed/25541298
My question is this: If someone is taking a PD-1 inhibitor, would it make sense to also supplement with this or is it akin to putting gas on a fire?
Thoughts?
My question would be how important are natural killer cells in glioma immunotherapy? They are apparently a very minor population within the immune infiltrate of GBM tumors.
ReplyDelete"According to our observations, NK
cells were one of the least numerous immune cell popula-
tions of all tumour infiltrating immune cells in glioblasto-
mas (2.11 % ± 0.54, mean ± SEM) and were
predominantly CD56dim CD16- [45]. These results are
based on multicolour flow cytometric phenotyping of
patients’ glioblastoma (GBM) tumour biopsies. The NK
cell population was defined as CD3 negative CD56 positive."
"In addition,
we examined the GBM biopsies for the presence of NK and B cells. They
were not very abundant and represented 2.11% ±0.54 and 0.66% ±0.27
(n = 8) of all tumor infiltrating immune cells, respectively. Within all
patients, NK cells were predominantly CD56dim CD16negative (Fig. 3K)
and 57.45% ±12.05 expressed the activating receptor NKG2D
(Fig. 3K). Six patients' biopsies were analyzed for the presence of type
I natural killer T-cells. However, they constituted only 1.13% ±0.65 of
all T-cells (data not shown)."
Second quote from: http://www.jni-journal.com/article/S0165-5728(13)00234-8/pdf
Most of the literature on glioma immunotherapy has focused on dendritic cells, CD3+/CD4+ T-helper and CD8+ cytotoxic T cells as opposed to natural killer cells, so this is an important question.
ReplyDeleteThat's something that I never considered. Thanks so much for this insight, as always. OK, one less thing to consider, which itself is helpful.
DeleteNK cells do only work if the tumor cells have no or low MHC expression. Examples of such tumors are neuroblastoma. In GBM, the more IFNgamma you have in the surrounding, the more MHC expression you will have, thereby making the tumor visible for CD8+ cytotoxic T cells (it works over MHC class I). If the tumor feel immune suppression in an immunological attack with cytokines amongst them INFgamma in the surrounding etc, they can try to escape the immune attack via expression of PDL1 that binds to PD1 of activated cytotoxic T cells. In this way the cytotoxic T cell activity is counter-regulated and the cytotoxic T cell will die. This is a natural downregulating balancing system in biology here used by the tumor. Nivolumab and Keytruda and other newer antibodies block the interaction between PDL1 and PD1, so block the downregulating balance allowing longer and stronger work of cytotoxic T cells in the immune response. Once again, these antibodies only work if there are antitumoral cytotoxic T cells active. That is why these antibodies do not always work in GBM patients.
ReplyDeleteThank you for the insights!
ReplyDeleteGoing back to Logan's original question ("If someone is taking a PD-1 inhibitor, would it make sense to also supplement with this or is it akin to putting gas on a fire?"), it's more as if you need to gather the materials to start the fire in the first place (if there is no spontaneous immune response against the tumor then you need to create one with, for example, a vaccine). But then it starts to rain and the fire almost goes out, and the PD-1 inhibitor is like a building a roof over the fire to keep the rain off.
Tumors like melanoma that have a higher mutational burden and are more immunogenic to begin with have a better chance of responding to PD-1 inhibitors as single agents. I suspect that many of the observed GBM responses to PD-1 or PD-L1 inhibitor monotherapy are potentially hypermutated (and thus more immunogenic) cases.
DeleteStephen W, this is precisely the question I have come to. PD-1 & PD-L1 inhibitors seem to work well in cases where killer cells abound, but in GBM they are sparse. My son is 3 transfusions since Jan 2019 of Keytruda into his therapy after prior 10X of whole head RT & refuses supplementation out of fear of being dropped from his Trial at Dana Farber. He is not doing well, with swelling, blurred vision, unsteadiness etc. Looking for something to upgrade the level of T Cells in his brain. Does this rice bran make sense to you. He is MGMT unmethylated, and Idh 1 & 2 Non-mutated.
ReplyDelete