[HN Gopher] Empty "backpacks" activate the immune system against...
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       Empty "backpacks" activate the immune system against cancer in mice
        
       Author : PaulHoule
       Score  : 71 points
       Date   : 2024-03-22 14:39 UTC (8 hours ago)
        
 (HTM) web link (medicalxpress.com)
 (TXT) w3m dump (medicalxpress.com)
        
       | vipa123 wrote:
       | Amazing what the frontiers science and medicine are doing...
        
         | PaulHoule wrote:
         | I love the term "backpack" and also how you can stick something
         | on a cell to reprogram it.
        
       | resource0x wrote:
       | In mice.
        
       | dopylitty wrote:
       | I always think of neutrophils as being like bombs full of bleach
       | roaming around looking to destroy things.
       | 
       | I wonder if these backpacks make them more likely to have off-
       | target effects since from the article it sounds like the
       | backpacks are putting the neutrophils in some sort of active
       | state. The paper isn't open access so I can't tell if this was
       | looked at.
        
         | hammock wrote:
         | >I always think of neutrophils as being like bombs full of
         | bleach roaming around looking to destroy things.
         | 
         | Pretty true and they're way more complex than that, as you
         | likely know.
         | 
         | They do ingest cells and then kill those ingested cells with
         | bleach (NADPH oxidase > superoxide > hydrogen peroxide >
         | hypochlorous acid). They also release at least 16 different
         | antimicrobial proteins into the surrounding environment. And
         | finally they release eutrophil extracellular traps (NETs), web-
         | like structures of DNA that trap and kill extracellular
         | microbes
        
           | dopylitty wrote:
           | I just finished reading this review from 2016 that was pretty
           | useful for summarizing what was known about neutrophils at
           | the time [0]
           | 
           | Even then they were known to be very complex with many
           | different phenotypes. I guess roaming bleach bombs wasn't the
           | most charitable description :)
           | 
           | 0: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225409/
        
           | Terr_ wrote:
           | There's a memorable bit from the book Immune [0]:
           | 
           | > This is what Neutrophils do when they create a Neutrophil
           | Extracellular Trap. Or NET for short. If Neutrophils get the
           | impression that drastic measures are called for, they begin
           | this crazy kind of suicide. First their nucleus begins to
           | dissolve, freeing up their DNA. As it fills up the cell,
           | countless proteins and enzymes attach to it--the sharp bone
           | splinters from our little story. And then the Neutrophil
           | literally spits out its entire DNA around itself, like a
           | giant net. Not only can this net trap enemies in place and
           | hurt them, it also creates a physical barrier that makes it
           | harder for bacteria or viruses to escape and move deeper into
           | the body. Usually the brave Neutrophil dies doing this, which
           | seems obvious.
           | 
           | > Sometimes, even though they vomited out their DNA, these
           | brave warriors continue to fight, throwing acid at enemies or
           | swallowing them whole and doing Neutrophil stuff before they
           | finally die of exhaustion. The question could be asked if a
           | cell that has given up its entire genetic material is still
           | alive. In any case, it can only go on for so long--without
           | DNA a cell has no way to maintain its inner machinery.
           | Whatever this cell is--a living entity or no more than a
           | zombie following its last commands mindlessly--it keeps doing
           | what it was made to do: It fights and dies for you, so you
           | can live. No matter which of its weapon systems it uses, the
           | Neutrophil is one of your fiercest soldiers and one that
           | enemies, and our own bodies, are rightfully pretty afraid of.
           | 
           | [0] https://www.penguinrandomhouse.com/books/669586/immune-
           | by-ph...
        
       | Zenzero wrote:
       | Unless they have plans to increase the specificity of these
       | activated neutrophils, this appears to have limited long term
       | usefulness.
       | 
       | Upregulating inflammatory cytokine expression in a nonspecific
       | manner like this has undesirable consequences. It is like having
       | a rat infestation in your home and your new solution is to add
       | some dynamite in with your rat traps.
       | 
       | Anyone who has managed cancer patients knows that downstream
       | effects of excessive/uncontrolled inflammation contribute
       | substantially to patient morbidity. Dysregulated edothelial
       | permeability, pleural and peritoneal effusion, coagulopathies,
       | glomerular injury, hypoproteinemia, hypotension, tumor lysis
       | syndrome... I could go on and on, but my point is there is a web
       | of interconnected problems you bring on board when you drive
       | inflammation.
       | 
       | The name of the game is isolated targeting of neoplastic cells in
       | a controlled manner that minimizes inflammation. That is very
       | difficult to do, but our best tools seem to be developing in the
       | fine-grained depths of immunology. Not strapping kamikaze
       | backpacks to neutrophils.
        
       | adamredwoods wrote:
       | Article:
       | 
       | https://wyss.harvard.edu/news/empty-backpacks-activate-the-i...
        
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