mRNAVille
One of the big deals in cancer research these days, for good reason, is the concept of immunotherapy.
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When you hear about this stuff it usually involves the immune checkpoint inhibitors like, say, nivolumab* which is a monoclonal antibody (the 'mab' part at the end of the name) that binds to and blocks the ability of 'checkpoint' molecules to suppress cells in the immune system, especially T-cells, from doing their job. Thus, these checkpoint inhibitors help the patient's own immune system to get going so that it can attack the tumour cells that it recognizes as foreign.
All of which is great news, and the treatments are getting better and better all the time.
But, still, they only work efficiently in a subset of 'hot' tumours that have lots of immune cells associated with them and that produce the checkpoint molecules, one of which is called PD-L1/CD274**. In addition, these antibodies/inhibitors aren't (at least not yet) very good at stopping the truly awful part of the disease that is metastatic spread.
The metastatic process begins when tumour cells escape from the place where they originate and travel or 'spread' to distant sites. This process is extremely inefficient and, upon arrival at the distant site the tumour cells very often sit dormant and do little or nothing from a pathology point of view, often for long periods of time. The real trouble begins when these dormant tumour cells wake up, start dividing like crazy, and become full blown, life-threatening metastatic lesions.
So, imagine if you could figure out how to keep these tumour cells at the distant site dormant. That knowledge could then be used to develop novel therapeutic strategies to keep the worst cancers in check without having to wallop the patient with classical 'slash and burn' drugs.
There have been a number of tantalizing nibbles on how to regulate tumour cell dormancy and most recently a group from Switzerland published a paper in Nature in June. These folks looked at all the mRNAs that are present in the dormant condition in experimental liver metastases and identified a suite of them that made the investigators think that the tumour cells were being bonked to sleep by a bunch of trigger-happy Woody Harrelson-like immune denizens called natural killer or 'NK' cells.
The Swiss group then identified the molecule that juices up the NK cells up to do the dormant cell bonking. What's really cool is that 'super agonists' that torque up the activity of this molecule, which is called IL-15, have already been developed. Thus, if this avenue of research can be translated to patients, and the Swiss group already has good 'correlational' data to support the notion, the approach could, potentially, be rapidly moved the clinic.
Man, I dig cell biology, even still, after all these years.
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Image at the top of the post is an NK cell in a culture dish getting ready to do its thing...The photo is from that place that Tony Fauci runs.
*The trade/pharma name of for nivolumab is 'opdivo'. There is actually a decent wiki page for it.
**Immunologists love to use acronyms, sometimes without apparent rhyme or reason to outsiders...As someone who is peripherally involved in the field it's a practice that drives me to distraction. In fact, I only half jokingly told a colleague recently that we could help them out with some culture assays as long I didn't have to memorize the 'CD' antigens. She did not laugh.
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