This is a pretty cool study with some interesting findings! Cancer immunotherapy has a long history but has become very prominent in recent years. (Fun fact: the senior author on this paper, Ed Engleman, co-founded of one of the first cancer cell therapy companies, Dendreon, in the early 90s). However, the success of immunotherapies has been limited by the immune-exclusionary nature of the tumor microenvironment (TME). Why some tumors are immune-hot and others are immune-cold is still a very open research question.
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.
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.
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.
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 ,
Do we understand the early dynamics of cancer? Do the hallmarks need to appear more or less at the same time by chance, or can the cancer cells acquire them sequentially, which would then induce a local microevolution process?
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.
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.
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:
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.
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".
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.
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.
This is a pretty cool study with some interesting findings! Cancer immunotherapy has a long history but has become very prominent in recent years. (Fun fact: the senior author on this paper, Ed Engleman, co-founded of one of the first cancer cell therapy companies, Dendreon, in the early 90s). However, the success of immunotherapies has been limited by the immune-exclusionary nature of the tumor microenvironment (TME). Why some tumors are immune-hot and others are immune-cold is still a very open research question.
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.
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.
> AFAICT there are no approved drugs blocking EPO receptors and no drugs to reduce EPO
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...
yeah i cannot read the full article
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.
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 ,
Do we understand the early dynamics of cancer? Do the hallmarks need to appear more or less at the same time by chance, or can the cancer cells acquire them sequentially, which would then induce a local microevolution process?
>>> generally, an organism with a malignant tumor is less likely to reproduce.
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?
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.
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.
6 replies →
The cancer problem always struck me as more of a control theory challenge than a purely biological one.
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
>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.
> ulcers are bacter
To be clear, some peptic ulcers are caused by H. pylori, but not all ulcers.
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.
2 replies →
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".
1 reply →
They do genetically sequence cancers today, at least looking for specific markers.
[flagged]
https://de.wikipedia.org/wiki/Alfons_Weber_(Mediziner,_1915)
Full paper link for the interested: https://ehdijrb3629whdb.tiiny.site
"404 Sorry, this content doesn't exist."
Let me guess, this research was sponsored by Lance Armstrong?
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.
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.
4 replies →