Wednesday, April 27, 2016

Celecoxib (Stuff that's in NSAID's like ibuprofen and aspirin!!!) and anti-PD1 work synergistically

I put this post up a while ago: An aspirin a day keeps melanoma at bay and makes immunotherapy work better???   As I noted in that post....I figure all us immunotherapy peeps have pretty much been living on advil in order to deal with our arthralgias!!!  But, this was republished recently:

Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumor immunity.  Li, Fang, Zhang, et al.  Oncoimmunology. 2015 Aug 12;5(2):e1074374. eCollection 2016. 

Two major challenges facing cancer immunotherapy are the relatively low therapeutic efficacy and the potential side effects. New drug delivery system and efficient drug combination are required to overcome these challenges. We utilize an alginate hydrogel system to locally deliver 2 FDA-approved drugs, celecoxib and programmed death 1 (PD-1) monoclonal antibody (mAb), to treat tumor-bearing mice. In two cancer models, B16-F10 melanoma and 4T1 metastatic breast cancer, the alginate hydrogel delivery system significantly improves the antitumor activities of celecoxib (CXB), PD-1 mAb, or both combined. These effects are associated with the sustained high concentrations of the drugs in peripheral circulation and within tumor regions. Strikingly, the simultaneous dual local delivery of celecoxib and PD-1 from this hydrogel system synergistically enhanced the presence of CD4+inteferon (IFN)-γ+ and CD8+IFN-γ+ T cells within the tumor as well as in the immune system. These effects are accompanied with reduced CD4+FoxP3+ regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) in the tumor, reflecting a weakened immuosuppressive response. Furthermore, this combinatorial therapy increases the expression of two anti-angiogenic chemokines C-X-C motif ligand (CXCL) 9 and CXCL10, and suppresses the intratumoral production of interleukin (IL)-1, IL-6, and cycloxygenase-2 (COX2), suggesting a dampened pro-tumor angiogenic and inflammatory microenvironment. This alginate-hydrogel-mediated, combinatorial therapy of celecoxib and PD-1 mAb provides a potential valuable regimen for treating human cancer.

Hmmmm.... "reduced myeloid derived suppressor cells (MDSCs)"....  Now that could be something!!  Remember this?   Increased Myeloid Suppressor cells = not so good.

And for what it's worth....there was also this back in the day:  
Nonsteroidal anti-inflammatory drugs and the risk of skin cancer:  A population-based case-control study. Johannesdottir, Chang, Mehnert, et al.  Cancer, 2012, May 29.

Knowing that Nonsteroidal anti-inflammatory drugs ( aspirin, ibuprofen, etc.) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, these folks from Denmark looked at NSAID use and the risk of squamous cell carcinoma, basal cell carcinoma, and melanoma.  They looked at all cases of those diseases from 1991 through 2009 in northern Denmark. (Squamous = 1,974, basal = 13, 316, and melanoma = 3,242).  They matched 10 population controls (n=178,655) to each case by age, gender, and county of residence.  Use of NSAIDs was noted via a prescription data base.  FINDINGS:  After a great deal of incidence rate ratios and confidence interval statistical shenanigans....they determined that "NSAID ever use compared with nonuse was associated with a decreased risk of squamous cell and melanoma, especially for long-term use and high-intensity use.  NSAID use was not associated with a reduced risk of basal cell.  All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors."

Just putting it out there.  Best - c


  1. I've been wondering why, after 17 years after having a melanoma removed from my nose, I ended up with melanoma tumors in my brain and lung. Could it be that the migraine headaches I'd been treating during the first 15 of those years saved me? I used to take Ibuprophen in large quantities several times a month to manage the pain. Post menopause the headaches went away, so no need for all those pain meds. It is disconcerting to think that those melanoma cells are so stubborn that they continue to survive in some small amount all that time, like the chickenpox virus, but great that continued use of NSAIDs can keep it at bay. Thankfully, my tumors arrived after immunotherapy treatments were invented and I'm responding nicely.

    1. Hard to say. I fear that advil is not really a cure nor preventative for melanoma. I think some of us either have a more active immune system than others or a more latent sort of melanoma. And, yes...melanoma is just that persistent, sneaky and stubborn. But....some of us are more so!!! So glad things are going well for you now.

  2. My Doc didn't tell me this, and I reduced my Celebrex usage in the last year, when brain tumors appeared. Back on the Celebrex...