Inflamation, PD-L1 and potential benefits of Curcumin.

[GrouseMan]

I just read a recent abstract of a paper found in the recent Science Signaling entitled:

Inflammation helps tumors evade immune detection see: http://stke.sciencemag.org/content/9/45 ... id=1064306

in this paper they demonstrate in mouse and other models that Inflammation in the tumor microenvironment has a direct effect on the abundance of the immune checkpoint ligand PD-L1 on the surface of tumor cells. They go on to determine that this is through a mechanism involving NF-kB activation which in turn may be correlated with stability of PD-L1. Inhibiting NF-kB via use of Curcumin at levels lower than those needed to kill a tumor, might still be clinically effective because it would inhibit NF-kB and reduce PD-L1 abundance.

Enjoy,

GrouseMan

[lpas]

Very, very interesting. Thanks for posting!

[plastikos]

Interesting indeed. Does this mean we should consider taking curcumun or turmeric while on PD-1 inhibitors? And at what dosage?

[GrouseMan]

Interesting indeed. Does this mean we should consider taking curcumun or turmeric while on PD-1 inhibitors? And at what dosage?

Much too early to tell on that one. This is really acting somewhat like a PD-L1 inhibitor, through upstream signaling . Its likely a weak inhibitor and unlike a PD-1 MAB inhibitor its not acting directly in PD-1 or PD-L1. The problem is the bioavailability of curcumin is not very good. Its not well absorbed. What someone needs to find is a much better NF-kB inhibitor than curcumin. However - I posed this as perhaps why this could be a reason some studies show the use of curcumin to be active against some cancers, particularly in the case as a potential preventative as so many studies have shown.

GrouseMan

[Maia]

- I posed this as perhaps why this could be a reason some studies show the use of curcumin to be active against some cancers, particularly in the case as a potential preventative as so many studies have shown.

Yes to that!
This article is great food for thought.
About taking curcumin before undergoing a treatment with a PD-1/ PD-L1 inhibitor, I was thinking the following: PD-1/ PD-L1 checkpoint inhibitors (pembro, nivo, atezo, durvalumab, avelumab, etc.) work better against tumours with *high* PD-1/ PD-L1 expression; that high expression predicts benefit from it, the drugs go against tissues with high values of PD-1 /PD-L1. And some trials run a test to determine PD-1/ PD-L1 expression, to determine inclusion.
So (and the following is more a question than an assert): might be that one doesn't want to "reduce PD-L1 abundance" before/when starting a therapy with this inhibitors, or at least maybe when initiating therapy with anti PD-L1 (the ones that go against the ligand on the surface of tumor cells, specifically, like atezo, durvalumab and avelumab; not pembro and nivo).
On the other hand, when already on an anti PD-L1, curcumin would add potency to the anti -pd-L1 one is taking?

And so nice to see you, GrouseMan! Happy your wife is doing quite well : )

[mtipte]

Really interesting! Curcumin is being part of many scientific studies now as I heard. What about using black pepper to boost its power? I read this in an anticancer book.

[mariane]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392790/

Do you know what were the results of this trial??

[Maia]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392790/

Do you know what were the results of this trial??

It is ongoing (https://clinicaltrials.gov/ct2/show/NCT01490996), they have not published results, that I could find. The study protocol is available here https://trialsjournal.biomedcentral.com ... 015-0641-1

[mariane]

Thank you very much Maia! You are true treasure!

[.jim.]

Really interesting! Curcumin is being part of many scientific studies now as I heard. What about using black pepper to boost its power? I read this in an anticancer book.

One of my wife's oncologists told her the way that black pepper increases bio-availability by causing inflammation in the gut, leading to 'leaky gut syndrome' which passes the curcumin (and other stuff?) into the bloodstream.

there are formulations that don't have pepper or bio-perine that have the curcumin bound to other molecules that help the get passed through the gut to the blood stream without doing it via inflammation.