7 ms·

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

186 points by daegloe 8y ago

rfinney 8y ago
Nature Medicine paper here : https://www.nature.com/articles/s41591-018-0135-2 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."
ArtWomb 8y ago
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 ;)
- ekianjo 8y ago
  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.
  - aswanson 8y ago
    Clinicaltrial.com sounds like a good url to plant the flag on this one.
  - Ntrails 8y ago
    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"
  - nonbel 8y ago
    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.
  - 1_over_n 8y ago
    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.
    - ekianjo 8y ago
      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.
  - Gibbous42 8y ago
    All clinical trials are listed and searchable on https://clinicaltrials.gov/ https://clinicaltrials.gov/
- aviv 8y ago
  There is already a built in "immunotherapy" in every single human body out there - it's called fasting. A prolonged, 40-day water fast will do far more good to the body than chemotherapy or any other man made invention ever will.
  - DrAwdeOccarim 8y ago
    You are wrong and you should feel bad. This is such a garbage statement. Anyone reading this who is dealing with or has a loved one dealing with cancer, don't listen to this non-sense. If this type of statement had truth to it, we would be all over it. The relationship between nutritional state and cancer is complex and it is dangerous to make blanket statements like this. Chemotherapy consistently works, that's why we use it.
    - dang 8y ago
      > You are wrong and you should feel bad Attacking someone like this will get you banned here regardless of how right you are. In particular, please don't use internet shaming tropes on this site. There are many ways to correct misinformation civilly and substantively; please use those instead. https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
      - DrAwdeOccarim 8y ago
        OK, sorry about that. Thanks for the pointer!
  - Broken_Hippo 8y ago
    If this was something that worked, it would be used. There is no reason for state-sponsored health care, insurance companies, and private individuals to use expensive treatments if someone could just go without food. I'd also like to point out that not only would it be against the interests of folks listed above, but it can easily be something that kills a patient. Doubly so if the person has diabetes, is malnourished, is a child or an infant.
- nonbel 8y ago
  >"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.
  - HeadsUpHigh 8y ago
    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.
    - nonbel 8y ago
      >"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.
      - HeadsUpHigh 8y ago
        Pathway is the official them used
    - 8y ago
- magicnubs 8y ago
  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.
  - ekianjo 8y ago
    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.
yhoneycomb 8y ago
(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
- newsbinator 8y ago
  I opened my closet to look for my boots and there they were: gone!
  - Amygaz 8y ago
    Gone! Where?
- war1025 8y ago
  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.
  - yhoneycomb 8y ago
    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."
- dibstern 8y ago
  I think they mean they found, in the bone marrow, an abundance of the missing T-cells (missing from the brain?)
- andyjohnson0 8y ago
  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.
tynpeddler 8y ago
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.

186 points by daegloe 8y ago

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

ArtWomb 8y ago

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 ;)

ekianjo 8y ago
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.
- aswanson 8y ago
  Clinicaltrial.com sounds like a good url to plant the flag on this one.
- Ntrails 8y ago
  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"
- nonbel 8y ago
  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.
- 1_over_n 8y ago
  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.
  - ekianjo 8y ago
    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.
- Gibbous42 8y ago
  All clinical trials are listed and searchable on https://clinicaltrials.gov/ https://clinicaltrials.gov/
aviv 8y ago
There is already a built in "immunotherapy" in every single human body out there - it's called fasting. A prolonged, 40-day water fast will do far more good to the body than chemotherapy or any other man made invention ever will.
- DrAwdeOccarim 8y ago
  You are wrong and you should feel bad. This is such a garbage statement. Anyone reading this who is dealing with or has a loved one dealing with cancer, don't listen to this non-sense. If this type of statement had truth to it, we would be all over it. The relationship between nutritional state and cancer is complex and it is dangerous to make blanket statements like this. Chemotherapy consistently works, that's why we use it.
  - dang 8y ago
    > You are wrong and you should feel bad Attacking someone like this will get you banned here regardless of how right you are. In particular, please don't use internet shaming tropes on this site. There are many ways to correct misinformation civilly and substantively; please use those instead. https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
    - DrAwdeOccarim 8y ago
      OK, sorry about that. Thanks for the pointer!
- Broken_Hippo 8y ago
  If this was something that worked, it would be used. There is no reason for state-sponsored health care, insurance companies, and private individuals to use expensive treatments if someone could just go without food. I'd also like to point out that not only would it be against the interests of folks listed above, but it can easily be something that kills a patient. Doubly so if the person has diabetes, is malnourished, is a child or an infant.
nonbel 8y ago
>"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.
- HeadsUpHigh 8y ago
  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.
  - nonbel 8y ago
    >"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.
    - HeadsUpHigh 8y ago
      Pathway is the official them used
  - 8y ago
magicnubs 8y ago
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.
- ekianjo 8y ago
  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.

yhoneycomb 8y ago

(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

newsbinator 8y ago
I opened my closet to look for my boots and there they were: gone!
- Amygaz 8y ago
  Gone! Where?
war1025 8y ago
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.
- yhoneycomb 8y ago
  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."
dibstern 8y ago
I think they mean they found, in the bone marrow, an abundance of the missing T-cells (missing from the brain?)
andyjohnson0 8y ago
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.

tynpeddler 8y ago

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.