[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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