Tumor-derived erythropoietin acts as immunosuppressive switch in cancer immunity
science.org
science.org
In this study, the authors demonstrate pretty convincingly that erythropoietin (EPO, a hormone that stimulates red blood cell production in the bone marrow) reduces the recruitment of tumor-cell-killing T cells to the TME. It does this by acting on tumor macrophages, another type of immune cell, and changes the state of these cells to facilitate accumulation of immunosuppressive cells.
They work out the mechanism largely through mouse models and associative analysis in human tissue samples, but I thought it was interesting that this finding aligns with the clinical observation that cancer patients who receive recombinant EPO for treatment of anemia frequently experience tumor progression.
After reading this, I am going back to check out EPO expression in old datasets that I worked with haha.
For others who might be curious, this study is genuinely good (evidenced somewhat by it being published in Science, as a study that is not in humans but still showing actual cancer curing efficacy not just some pathway finding) is that they use difficult but necessary model systems that emulate real tumor environments - these are spontaneous tumors that show up in mice that have full immune systems. Literally 99.9% of cancer study papers don't use such systems and in my opin9on get fully invalidated for most interpretation.
Anyways I'm curious if the microenvironment will just evolve quickly to be EPO independent, as it typically seems to do something like that in real long term tumor environments you encounter in people compared to mouse models.
But at face value this looks very promising.
This identifies one way solid tumors avoid immune attack and identifies corresponding therapeutic targets that could span solid tumor types.
EPO (erythropoietin) (aside from stimulating red-blood-cell production) also converts tumor-local macrophages from attacking to suppressing immune attacks. Tumors are shown to produce EPO themselves.
Tumors spontaneously regressed due to revived immune response when blocking either EPO or the EPO receptor on the macrophages.
The model was murine liver cancer, but high blood EPO levels are known to be poor prognosticators in many solid tumor cancers.
This summary points to NRF2 (nuclear factor erythroid 2-related factor 2) as a regulatory target, but without any detail.
AFAICT there are no approved drugs blocking EPO receptors and no drugs to reduce EPO; there are some anti-anemia drugs that increase production.
Such receptors have a protein structure definitive for them, so a bespoke RNA (mRNA) therapy might be a means of generating receptor blockers?
Edit: looks like this applicable. two interesting articles...
https://pubmed.ncbi.nlm.nih.gov/28629523/
https://www.genengnews.com/topics/cancer/blocking-erythropoi...
We know some cancers can be caused by viruses. And we know a few cancers that act like viruses in dogs and Tasmanian devils, and some rare cases in humans.
We only figured out that ulcers are bacterial in origin within the lifetimes of many HN readers, and there are signs that other GI issues may be bacterial or viral (or bacteria-targeting viral) as well.
Maybe we need to start culturing and DNA testing cancers.
Most scientists wouldn't call the hallmarks of cancer "evolution". I think instead most would say that cancer is an almost certainly unavoidable outcome of the complexity of eukaryotic organism's control of cellular replication.
There's a series of papers organized around the "Hallmarks of Cancer" which help explain why nearly all tumors show the same properties- and how they are effectively due to dysregulation of evolutionary checkpoints and signalling. generally, an organism with a malignant tumor is less likely to reproduce. However, it's really far more complex than that ,
Huh?
What is meant by this? Like if you have cancer, you are less likely to want to reproduce? Or, less likely to reproduce due to the illness?
"Maybe we need to start culturing and DNA testing cancers." I assure you this is being done at a massive scale.
Due to cellular stress, cancer cells disobey multi-cellular governance. They behave more like independent organisms fighting for survival, reverting to primal programming.
I was trying to remember which mammal in Australia gets tumors from fighting, and I found a reference to a mother getting melanoma from her daughter. It’s unclear to me whether the cancer transmission was rare or the identification is rare.
Transmission of cancer is rare in humans—if it were not, it would make someone’s career to find many cases of it. While we can’t say that all sheep are white, we’ve looked at enough of them to say that black sheep are not common. Furthermore, it’s very clear how the Tasmanian devil cancer is spread—it’s around the mouth while they are biting each others faces; it’s not as obvious how one would spread most human cancers.
Cancers with established viral etiology or strong association with viruses include:
- Cervical cancer - Burkitt lymphoma - Hodgkin lymphoma - Gastric carcinoma - Kaposi’s sarcoma - Nasopharyngeal carcinoma (NPC) - NK/T-cell lymphomas - Head and neck squamous cell carcinoma (HNSCC) - Hepatocellular carcinoma (HCC)
One cell's DNA damage is another cell's evolution.
To be clear, some peptic ulcers are caused by H. pylori, but not all ulcers.
Also don’t abuse advil, kids. OTC painkillers can burn a hole in your digestive tract. I in fact know someone missing a few feet of intestine because of chronic back pain and overuse of non narcotic painkillers.
That's worldwide. In developed countries the proportion is closer to 10 to 15% [1, 2]
[1] https://www.jwatch.org/na50875/2020/02/24/prevalence-h-pylor...
It’s a stress-signaling hormone produced by the kidneys when they detect hypoxia and triggers more red blood cell production in bone marrow.
Obviously, that didn't work, but I guess he was just ahead of his time. These days, he could have run for president.
That's not how I read this part of the Wikipedia article[1]:
> In June 2012, USADA accused Armstrong of doping and drug trafficking, based on blood samples from 2009 and 2010
[1] https://en.wikipedia.org/wiki/Lance_Armstrong_doping_case#20...
But they were also using “blood doping” which is essentially giving blood transfusions to yourself. One of his lieutenants, Tyler Hamilton, got busted for it a few years before Lance got caught. He claimed he was innocent and maybe it was chimerism or an absorbed twin. But this dumb fucker had already been caught doping several times before, one of which stuck and the other failed on a technicality (frozen backup sample could not be tested) My guess is they switched bags and he’s lucky he got a compatible bloodtype and didn’t stroke out. He got caught doping again in 2009 and received an 8 year ban, and retired. And later was stripped of his gold medal as well.
The only legal form of blood doping is altitude training and that effect doesn’t last long enough for the Tour or the Gira. But could allow someone to get an early lead.
As for Lance not getting caught between 1998 and 2005, that’s only barely technically true. He was caught using corticosteroids in a test in 1999, but explained it away with a topical steroid allegedly for saddle sores. He confessed later that it was a cover up for his doping. He also tested positive for EPO six times during this period but as the tests were still experimental, there was some clever lawyering that kept it from sticking.
Laurent Fignon and Eddie Merckx have both been accused of stimulant use which cost them only one or two races instead of years.
Richard Virenque was a popular French rider who won the King of the Mountain many many times, when he went down it was for an entire cocktail of drugs including HGH.
And I had forgotten that Christian Vande Velde was caught in the postal service bust. He’s a commentator for NBC now. I wonder what Liggett thinks of that.
Sources: a bit of memory but mostly https://en.wikipedia.org/wiki/List_of_doping_cases_in_cyclin... which, by the way, has become ridiculously, alarmingly long. Jesus Christ.
There is a mountain of evidence that the drug cheating was systematic. You can read The Secret Race, or draw your own conclusions from the $5 million false claims act settlement.
And they’ve discovered in more recent studies that steroid use has effects that last about twice as long as it’s detectable in your body (2 vs 1 year?). If sports weren’t such a young person’s game, I’d worry about people taking off for “surgery” and coming back built like a linebacker but testing clean.