Friday 15 July 2016

Checkpoint blockade and Cox 2 inhibitors

Since it is becoming increasingly evident that inflammation can be beneficial to enhanced immune response when using checkpoint inhibitors, I am wondering if it might be prudent to discontinue celebrex and possibly even EFA's (fish oil in this case), in an attempt to enhance the immune response.  Any thoughts on this?
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6 comments:

  1. Stephen W15 July 2016 at 11:54

    "Inflammation" is such a vague word I try not to even use it. There are different types of inflammation, as there are different types of immune responses, some are tumor-promoting, some tumor-suppressing.

    There have been at least two (perhaps more) mouse studies showing that a drug such as Celebrex actually synergizes with PD-1 antibodies. Celebrex inhibits the production of prostaglandin E2 (PGE2), which is an important immunosuppressive molecule.

    http://www.cell.com/cell/abstract/S0092-8674(15)01028-4

    http://www.ncbi.nlm.nih.gov/pubmed/27057439

    There are also an number of mouse studies showing co-operation between celebrex and various anti-tumor vaccines.

    The evidence is more mixed for the long-chain omega 3 fish oils like EPA and DHA. I'm preparing the evidence to write an article or update on some of the potential immunosuppressive effects of common anti-cancer supplements. There is a document in folder 0 of the brain tumor library called "Immunological effects of commonly used supplements" where I'm compiling the information.

    One study I linked there is called "Docosahexaenoic acid prevents dendritic cell maturation, inhibits antigen-specific Th1/Th17 differentiation and suppresses experimental autoimmune encephalomyelitis". This was not a cancer model, but preventing dendritic cell maturation is not something you particularly want if pursuing cancer immunotherapy. I've also seen studies on the positive side of the equation for DHA. Notice also potential immunosuppressive effects of THC (from cannabis), and there is mixed evidence about immunosuppression/activation for CBD (promotion/suppression of Th1 type responses, or active CD8+ T-cell responses being my definition of the above categories).

    Short answer: I would certainly not discontinue Celebrex, but I would consider going easy on the fish oil, esp around the time of therapy with nivolumab or other immunotherapies.

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  2. Michael W15 July 2016 at 15:27

    thank you Stephen.

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  3. linda15 July 2016 at 21:55

    Stephen, what are your thoughts on about taking chloroquine and Pd1 inhibitors together?

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    1. Stephen W15 July 2016 at 23:05

      Definitely mixed evidence for chloroquine's effect on immunity.

      PRO:

      Primary CD8+ T-cell response to soluble ovalbumin is improved by chloroquine treatment in vivo
      http://www.ncbi.nlm.nih.gov/pubmed/18753338

      Blocking Hypoxia-Induced Autophagy in Tumors Restores Cytotoxic T-Cell Activity and Promotes Regression
      http://www.ncbi.nlm.nih.gov/pubmed/21810913

      However the use of chloroquine in autoimmune conditions shows it can have immunosuppressive effects as well. It is likely context-dependent, and there really hasn't been enough study of chloroquine modulation of the immune system in the cancer setting save for one or two studies. It's a tough call...

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  4. linda18 July 2016 at 04:40

    Thanks Stephen, Probably will go off chloroquine if considering a PD1 inhibitor.... Chloroquine has such along half life too. No easy decision.

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  5. Unknown19 July 2016 at 14:41

    Extremely helpful post Stephen. Thank you very much.

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