Duke Team Finds Missing Immune Cells That Could Fight Lethal Brain Tumors | Hacker News Reader

Duke Team Finds Missing Immune Cells That Could Fight Lethal Brain Tumors

corporate.dukehealth.org

186 pointsdaegloe34 comments

The mechanism by which a tumor suppresses and evades immune response is tremendously complex. And while directly "locking" helper cells in bone marrow may seem a most pernicious defense. It isn't the only one.

For immunotherapy to fulfill its promise. Every type of response for every category of tumor cell must be decoded. As well as every effective ligand to boost immune cell strategy.

Currently there are only a handful of therapies approved globally. Among hundreds of ongoing trials that need patients to sign up.

The inefficiency in the marketplace landscape then is a disconnect. Between patients for whom there may be a potential cure. And researchers who lack the reach to connect with them.

There is probably potential for a startup here that connects the two ;)

The problem is that clinical trials are pretty much not advertized to the public and rely on very inefficient doctor networks to find patients. It like the middle ages.

Clinicaltrial.com sounds like a good url to plant the flag on this one.

I think advertising clinical trials to the public is actively prevented due to the tremendous uncertainty around both patient suitability and treatment risk/efficacy. This needs to be something that is managed by an expert in the middle who can assess these factors rather than just telling everyone "Talk to your doctor about miracle cure X, see if it's right for you".

I'd argue that the correct step forwards is improving the aformentioned "inefficient doctor networks"

People have a really wrong idea about "experimental" medical treatments.

Its much easier to break something you don't understand than fix it, and our knowledge of the human body is so rudimentary it is effectively zero. The only way to check what will happen is to try it.

The only comfort for the first humans being injected/whatever with something is that nothing too awful (relative to the problem being addressed) happened to some mice/rats/primates in the short term.

Also, consider that a clinical trials for Cancer may not be a first line therapy or ideal choice - it's often something that people who are desperate and at an advanced stage consider due to their options running out.

Yes, but even late stage patients don't have too many options because clinical trials are usually designed to follow very specific algorithms of treatments and reject patients who don't exactly fit in. So there is actually a lot of friction in the current system, and the fact that clinical trials are typically expensive for companies to run just exacerbates things.

All clinical trials are listed and searchable on https://clinicaltrials.gov/

>"The mechanism by which a tumor suppresses and evades immune response is tremendously complex."

What is so complex about it?

>"Every type of response for every category of tumor cell must be decoded. As well as every effective ligand to boost immune cell strategy."

Why? Also, the "categories of tumor cell" are arbitrary. The categories are chosen by humans for ease of communication and understanding. You can have as many or as few as you want.

Think hundreds if not more different pathways utilizing many different mechanisms that are not even mapped that well. Anything from external to the cell molecules to internal ones to noise based ones. And then add on top of that variations in tumor topography and variations in each tumor type that make some people with the same cancer react to a drug really well while others don't.

Also no categorization in medicine is arbitrary ( or at least almost none). Everything on a clinical level is categorized based either on how it's best diagnosed or cured, for example a cancer might be categorized as a small cell lung cancer when it comes to chemo but use a different classification scheme from radiologists when surgeons are concerned because they care about the area of effect instead ( in both cases a cure based taxonomy). The small cell cancer has different molecular signatures than e.g. non small cell types which means it will react differently on specialized antibody therapies.

This taxonomy is nowadays expanding rapidly based on new drugs and studies on which variations of proteins they are effective.

>"Think hundreds if not more different pathways utilizing many different mechanisms that are not even mapped that well."

Perhaps "pathways" isn't the right way to think about whats going on if it makes it seem so complex.

Pathway is the official them used

>"Also no categorization in medicine is arbitrary ( or at least almost none)."

Ok, this is crackpot.

IQVIA (and I'm sure other CROs as well) is spending a fair chunk of change focusing on improving their offering in this space right now. Will be interesting to see if anything comes of it.

I hope that IQVIA's efforts in that field are better than their typical data management practices, because they are pretty horrible at what they do usually. I would not trust them much based on what I have seen.

Nature Medicine paper here : https://www.nature.com/articles/s41591-018-0135-2

"Sequestration of T cells in bone marrow is therefore a tumor-adaptive mode of T cell dysfunction, whose reversal may constitute a promising immunotherapeutic adjunct."

(from the second image)

"Duke scientists discovered an abundance of missing T-cells trapped within the bone marrow."

"an abundance of missing"

I know everyone makes mistakes, but I can't even fathom writing this sentence and thinking it sounded good

I opened my closet to look for my boots and there they were: gone!

Gone! Where?

I guess it sounds alright to me? I didn't read the article, so I might be missing the context, but it sounds like there were fewer T-cells than they thought there should be, and they found that a bunch of them were in the bone marrow when they didn't expect it.

Oh... yeah that makes sense now. Very confusing wording though. I thought that they were ONLY saying "there were a lot less T-cells in the bone marrow."

I would have said: "Increased T-cells were found trapped in the bone marrow, a possible explanation for the decreased T-cells in the brain."

I think they mean they found, in the bone marrow, an abundance of the missing T-cells (missing from the brain?)

It reads ok to me (English speaker).

The T cells were missing from the brain and the rest of the body because they were trapped in the bone marrow.

Abundance of cells. This is a properly formed English sentence.

I think it reads fine, especially in context. It could be restated, "The missing T-cells were discovered, in abundance, trapped within the bone marrow."

Is it possible that glioblastoma cancer is a result of two different dysfunctions? The glioblastoma tumor in the brain, and an unrelated sequestration of T cells in the bone marrow?

The abstract states that the loss of S1P1 is tumor imposed, but not having access to the paper, I don't know what they mean by that.

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