Inflamation, PD-L1 and potential benefits of Curcumin.

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GrouseMan
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Inflamation, PD-L1 and potential benefits of Curcumin.

Postby GrouseMan » Tue Dec 20, 2016 4:56 pm

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
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
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8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
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8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
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lpas
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby lpas » Tue Dec 20, 2016 9:37 pm

Very, very interesting. Thanks for posting!
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plastikos
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby plastikos » Wed Dec 21, 2016 12:52 am

Interesting indeed. Does this mean we should consider taking curcumun or turmeric while on PD-1 inhibitors? And at what dosage?
St. IV Colon CA @ 37, male, Kras wild, MSI-high (2014)
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GrouseMan
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby GrouseMan » Wed Dec 21, 2016 11:27 am

plastikos wrote: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
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017

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Maia
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby Maia » Wed Dec 21, 2016 12:17 pm

GrouseMan wrote:- 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
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby mtipte » Wed Dec 21, 2016 4:23 pm

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.

:)
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mariane
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby mariane » Fri Jan 27, 2017 5:58 pm

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

Do you know what were the results of this trial??
mom of now 10 years old twins, dx @ 40 in 6/2015 with upper rectal cancer, 10+ liver mets, CEA 140
chemo: 8/2015 - 10/2016 - 4xFOLFIRINOX, 2xFOLFOX, 8xFOLFIRI, 10x5FU, HAI pump -12xFUDR
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Maia
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby Maia » Sat Jan 28, 2017 6:33 am

mariane wrote: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
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby mariane » Sat Jan 28, 2017 8:52 am

Thank you very much Maia! You are true treasure!
mom of now 10 years old twins, dx @ 40 in 6/2015 with upper rectal cancer, 10+ liver mets, CEA 140
chemo: 8/2015 - 10/2016 - 4xFOLFIRINOX, 2xFOLFOX, 8xFOLFIRI, 10x5FU, HAI pump -12xFUDR
4 surgeries, complete pathological response
CEA<2 since 10/2015
NED since May 2016

I praise God for every day with my family!

.jim.
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Re: Inflamation, PD-L1 and potential benefits of Curcumin.

Postby .jim. » Sat Jan 28, 2017 11:01 pm

mtipte wrote: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.
husband to DW stage IV MSS KRAS-wt BRAF-wt
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12-2016 pet scan shows activity in liver and new mets in lungs
1-2017 cea rising; chemo folifiri-avastin stopped
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