Sunday, 18 September 2016

Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810449/

12 comments:

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    1. misread the "suppress"...I do agree with Stephen's below point.

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  2. I was looking at this study in context for using with a PD1 inhibitor and the study suggests the possibility of immunotherapy for immunosuppression, using curcumin and resveratrol by selective regulation of CTLA-4, CD28, CD80 and IL-10 which I thought would negatively impact a PD1 protocol. Any thoughts anyone??

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  3. Hello,
    I am a bit confused now...isn't suppressing immune response a bad thing - or in other words, isn't this article "against" taking curcumin and resveratrol?

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    1. On the surface, this study does seem to be saying that curcumin and resveratrol are immunosuppressive (stimulating the immune checkpoint CTLA-4 and downregulating CD28), which wouldn't be desirable in a cancer setting. However, I don't really trust this data, see my comments below.

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  4. 1. This was in an vitro study. In vitro studies using higher-than-physiological concentrations of drugs isn't a reliable guide to the effects of these drugs in vivo with much lower concentrations.

    In vivo studies with tumor-bearing animals (or human studies where those exist) is a better indicator of how the agents might behave in vivo. For example there are several studies showing curcumin stimulates cell-mediated immune responses in tumor bearing animals.

    The bigger problem is that many agents can have both immune-stimulating and immune-suppressing effects, depending on the context. Most agents have not been tested in combination with cancer vaccines, so there's actually no data to understand what the effects might be.

    There are human studies showing that curcumin lowers levels of STAT3, which is an important pro-tumor and immunosuppressive transcription factor.

    There was at least one in vivo study showing curcumin can improve the efficacy of a vaccine in a melanoma mouse model.
    http://www.ncbi.nlm.nih.gov/pubmed/26305550

    In my view tumor-bearing animal models provide superior evidence than in vitro studies using supra-physiological drug concentrations.

    I've been compiling the evidence in a document in the Library (folder 0) called "Immunological effects of drugs/supplements".

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    1. Hi Stephen, I read the "immunological effects" document and noticed that resveratrol may be immunosuppressive and prevent rejection of allografts.

      Can you elaborate on how this should or could be interpreted? Is an allograft comparable to a cancer tumor and thus resveratrol supplementation could be detrimental?

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    2. This is a really important question, and is the subject of a study I've been meaning to read:

      https://www.ncbi.nlm.nih.gov/pubmed/27529775

      I'm going to read this today and will comment if it clarifies this issue at all.

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    3. This was a general review trying to increase understanding of graft rejection by studying the work of oncoimmunologists and drawing parallels between the two fields.

      "At least, the 4 therapy-induced mandatory factors to
      promote tumor ICD (CALR, eATP, HMGB1, type I IFN/CXCL10) have been shown to be implicated in IRI as well." Where ICD refers to immunogenic cell death and IRI refers to ischemia-reperfusion injury, a common occurrence in organ transplants.

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    4. Thank you Stephen! Not sure how to interpret your quotation though? I interpret it as allograft rejection vs tumor promotion being very similar in nature, but am unable to decipher the rest of it, i.e. may resveratrol, boswellia and the like do more damage than good?

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    5. It does make you think twice about basing treatment decisions on xenograft mouse models performed with immunodeficient mice lacking T-cells, where the immunological effects are left out of the equation.

      I'm not sure I would say they do more harm than good. They may also have anti-tumor effects (or anti-edema effects in the case of Boswellia) that have to be weighed against immune effects. This question becomes larger when the patient is pursuing active immunotherapy such as a vaccine. Then one needs to be really careful that supplements are not limiting the immune response.

      On the whole this question is understudied. With all the mouse studies testing various immunotherapies and vaccines there are almost no studies combining immunotherapies with supplements/repurposed drugs to see how that effects the immune response. It's really hard to say anything definitive about this question given the absence of direct evidence.

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  5. Thanks Stephen, I thought it was a mouse study, didn't realise that they sacrificed the mice and only used it's cells. Must read these studies more carefully.

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