[HN Gopher] Tumor-derived erythropoietin acts as immunosuppressi...
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       Tumor-derived erythropoietin acts as immunosuppressive switch in
       cancer immunity
        
       Author : bookofjoe
       Score  : 97 points
       Date   : 2025-04-25 14:42 UTC (8 hours ago)
        
 (HTM) web link (www.science.org)
 (TXT) w3m dump (www.science.org)
        
       | w10-1 wrote:
       | It would be nice to see the original article.
       | 
       | 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.
        
         | badmonster wrote:
         | yeah i cannot read the full article
        
       | mariusor wrote:
       | Let me guess, this research was sponsored by Lance Armstrong?
        
         | hinkley wrote:
         | Huh. I assumed this was going to be a collision of acronyms but
         | erythropoietin is the same EPO used medicinally to treat anemia
         | and abused by several generations of endurance athletes
         | (complications include strokes and heart attacks from blood
         | clot).
         | 
         | It's a stress-signaling hormone produced by the kidneys when
         | they detect hypoxia and triggers more red blood cell production
         | in bone marrow.
        
           | mariusor wrote:
           | What makes this mildly funny, though I admit in quite poor
           | taste, is the fact that Armstrong did indeed suffer of cancer
           | to which he lost a testicle before his comeback to win
           | multiple Tour de France back to back. So theoretically his
           | EPO positive results could be attributed to those tumors
           | producing it, if this research is to be believed. Maybe not
           | all of the times though.
        
             | hinkley wrote:
             | He was on steroids post treatment as well. Chemotherapy
             | likes to cause anemia. In fact I think that's where I first
             | heard of EPO. Some survivor crowing about the efficacy at
             | making them feel human again.
             | 
             | 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.
        
             | nonameiguess wrote:
             | Lance Armstrong never failed a drug test. The CEO of the
             | insurance company responsible for underwriting bonus
             | payments for Tour de France wins had read a book full of
             | circumstantial evidence of the US Postal Service team
             | doping and contested paying out the bonus. He knew they'd
             | lose, but wanted to force the hands of some investigative
             | body with real power to actually look into it. Federal
             | prosecutors took up the case for a couple years, but then
             | dropped it. Then USADA finally got a bunch of his former
             | teammates and medical staffers to testify against him.
             | Lance didn't even contest the finding because the evidence
             | was so overwhelming, he figured his best course of action
             | at that point was trying to keep the report confidential
             | and winning in the court of public opinion instead,
             | convincing all of his adoring fans that he was the victim
             | of a witch hunt.
             | 
             | Obviously, that didn't work, but I guess he was just ahead
             | of his time. These days, he could have run for president.
        
       | hinkley wrote:
       | Tumors excreting chemicals to prevent destruction doesn't sound
       | like DNA damage, that sounds like evolution.
       | 
       | 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.
        
         | Kalanos wrote:
         | You're right, DNA damage is just one of the types of genetic
         | variation in cancer. There are many other structural variations
         | that act like remixes.
         | 
         | "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.
        
           | hinkley wrote:
           | Oh I know we are trying to genomically test them for oncology
           | research and potential treatment plans, but do they do
           | paternity tests on them?
           | 
           | 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.
        
             | rflrob wrote:
             | There's very often a comparison to the somatic (i.e. non-
             | cancer) genome of the same patient. It's a great way to
             | quality control that there wasn't some sample mixup in the
             | lab.
             | 
             | 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.
        
               | hinkley wrote:
               | Oh that makes sense. I forgot about differential
               | analysis.
        
               | jjtheblunt wrote:
               | Is HPV an example?
        
               | cogman10 wrote:
               | Not really. It's a virus that can cause cancer and not
               | the cancer itself.
        
             | dekhn wrote:
             | tasmanian devils [edit: I guess you already said that]
             | https://en.wikipedia.org/wiki/Devil_facial_tumour_disease
        
               | hinkley wrote:
               | Yup. Link is handy though. Someone will post it to the
               | front page in 14 hours :)
        
           | superfist wrote:
           | The cancer problem always struck me as more of a control
           | theory challenge than a purely biological one.
        
         | giantg2 wrote:
         | They do genetically sequence cancers today, at least looking
         | for specific markers.
        
         | atombender wrote:
         | > ulcers are bacter
         | 
         | To be clear, _some_ peptic ulcers are caused by _H. pylori_ ,
         | but not all ulcers.
        
           | dekhn wrote:
           | Yeah the real outcome of all this was "stress is not a cause
           | of ulcers and other GI issues, but it can increase the
           | negative impact" and "some uclers and other GI issues can be
           | treated by antibiotics".
        
           | hinkley wrote:
           | The guy who won the Nobel prize for giving himself an ulcer
           | estimated it as 90%, which is very comfortably "most". If
           | that has been drastically estimated down I hadn't heard.
           | 
           | 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.
        
             | jjtheblunt wrote:
             | I did the oops too much Advil on myself naively over years.
             | Gastritis and resolves once the cause is figured out but
             | scared me to respect otc meds more.
        
         | dekhn wrote:
         | We already culture and DNA test cancers. Sometimes we can point
         | at a secondary tumor and say "it came from this primary tumor".
         | And we already know viral and bacterial infections can increase
         | the likelihood of people getting malignant tumorws.
         | 
         | 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 ,
        
         | atahanacar wrote:
         | >Tumors excreting chemicals to prevent destruction doesn't
         | sound like DNA damage, that sounds like evolution.
         | 
         | One cell's DNA damage is another cell's evolution.
        
         | panabee wrote:
         | To provide more color on cancers caused by viruses, the World
         | Health Organization (WHO) estimates that 9.9% of all cancers
         | are attributable to viruses [1].
         | 
         | 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)
         | 
         | [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC8831861
        
         | rundmc wrote:
         | Cancer is parasites.
         | 
         | Tumours are dormant egg sacs that the body has encased to
         | control the spread of the babies.
         | 
         | Biopsies puncture the encasement and release the babies causing
         | the 'cancer' to spread.
         | 
         | All of the research proving the above can be found on X.
         | 
         | What a shame that the scientists developing treatments for the
         | symptoms are still blinded to the root cause when the rest of
         | the world has woken up to the fraud being perpetrated upon us.
        
       | SimplyUnknown wrote:
       | Full paper link for the interested:
       | https://ehdijrb3629whdb.tiiny.site
        
         | damnitbuilds wrote:
         | "404 Sorry, this content doesn't exist."
        
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