Is IL-33 expression a key to risk for prostate cancer progression and metastasis?


According to a newly published article in the journal Scientific Reports, men who lose normal expression of a protein known as interleukin-33 or IL-33 are at higher risk for recurrence of their prostate cancer within 5 years than men who do not lose the expression of this biomarker.

The original paper by Saranchova et al. can be found if you click here, but many readers may find this information a little difficult to interpret. The associated commentary on the ScienceDaily web site might be rather easier to follow. However, the title of the commentary on the Science Daily web site (“How cancer’s ‘invisibility cloak’ works”) needs to be taken with a large dose of realism in order to manage the hype. We don’t yet know that that title is correct.

Basically, Saranchova et al. are suggesting that, in epithelial carcinomas (i.e., cancers that start in the tissues that line the surfaces of organs like the prostate, kidney,breast, lung, uterus, cervix, pancreas, and others), loss of expression of the IL-33 protein seems to be associated with a high likelihood that these cancers will recur after first-line treatment.

Expression of IL-33 is closely associated with the ability of our immune systems to recognize and act against cancer cells, so when IL-33 is not being expressed our bodies have no way to recognize the cancer cells and so those cells can grow, start to spread, and potentially metastasize.

When the research team conducted laboratory studies to “put back” IL-33 into tissues from metastatic cancers in which IL-33 was not normally being expressed, they were able to revive the ability of the tissues’ immune system to recognize and “fight back” against the cancers.

Now this is potentially a very exciting finding. If lack of expression of the IL-33 protein really is a critical factor in the initiation of the spread of cancer, and — conversely — if expression of the IL-33 protein can ensure activation of the immune system to suppress the growth of cancer cells (and prostate cancer cells in particular), then if we can find a way to stimulate expression of the IL-33 protein in men diagnosed with certain types of prostate cancer we may be able to re-suppress that cancer.

However … We also need to keep our expectations reasonable. What we really have here is a pair of related hypotheses:

  1. That levels of expression of the protein IL-33 may be an indicator of risk for recurrent and metastatic disease in men with prostate cancer.
  2. That re-stimulation of the expression of Il-33 in men with prostate cancer who who have stopped expressing IL-33 may be an effective form of treatment for certain types of high-risk prostate cancer.

It will take a lot of work to validate the first hypothesis. It will take even more work to test and validate the second hypothesis. And we know that, historically, very little is simple in the diagnosis and management of prostate cancer … but then “hope” does indeed “spring eternal”.

One Response

  1. As you indicated, excitement about IL-33 is premature, but this does look interesting. (Okay, just whispering here, I’ll admit I’m excited.)

    Yes, that paper is a bit of a challenge, but for a quick teaser version searching for prostate cancer and also starting with the Discussion section may help.

    Here’s what most caught my attention in the Discussion section: “… In addition, we demonstrate that IL-33 down-regulation [meaning reduced to a lower level, such as when compared in metastatic cells versus normal cells or cancerous non-metastatic cells] is significantly associated with reduced survival time in human prostate cancer (97 months compared to 56.7 months)….” Wow! Here’s another striking sentence: “… Overall the down-regulation of IL-33 takes place concomitantly with the transition from primary to metastatic tumours and represents an entirely new form of tumour immune-escape. …”

    I was impressed that this work was done in British Columbia, home of the renowned “Vancouver Prostate Center,” and that one of the co-authors was Dr. Martin Gleave, MD, whose work and institution are well known to so many of us. This is far from his first rodeo, and his enthusiasm, as reflected in this paper, is, in itself, exciting.

    How wonderful it would be if this panned out with a practical way to make up for IL-33 deficiency in metastatic prostate cancer patients. It could lead to enormous breakthroughs in improved survival and even cures. It could make other treatments, such as Provenge, and combinations of treatments much more effective.

    Thanks for posting this!

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