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.
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.
>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
> 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.
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.