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.

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.

Full paper link for the interested: https://ehdijrb3629whdb.tiiny.site