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taylorvich [soylentnews.org] writes:

https://newatlas.com/medical/rac2-protein-macrophages-cannibalize-t-cells-cancer-immunotherapy/ [newatlas.com]

Following a trail of evidence that started with a study of fruit flies nearly 25 years ago, researchers have found adding a hyperactive form of the protein Rac2 to macrophages, immune cells that eat pathogens, causes them to cannibalize T cells. The novel technique could potentially boost the effectiveness of an emerging cancer treatment.

Rac proteins have been around for a long time. Deeply conserved in evolution, the proteins are thought to have been present in the earliest nucleated cells. But, despite their age, scientists are still uncovering their mysteries. In a new study, researchers from the University of California Santa Barbara (UCSB) discovered more about how Rac proteins work and how they could potentially improve cancer treatment.

The human genome encodes three Rac proteins. Rac1 is expressed ubiquitously, Rac2 is expressed predominantly in cells that produce blood components (hematopoietic cells), and Rac3 is expressed primarily in brain tissue. Back in 1996, researchers studying fruit flies found that the proteins were instrumental in cell movement and that a hyperactive form of Rac1, expressed in only a few cells in a fly’s egg chamber, destroyed the whole tissue.

“Just expressing this active Rac in six to eight cells kills the entire tissue, which is composed of about 900 cells,” said Abhinava Mishra, the current study’s lead author.

That was as far as the researchers got in the ’90s. It wasn’t until a few years ago that research started to emerge suggesting that cannibalism might be the cause of this tissue destruction.

In 2019, a study published in the journal Blood reported on three unrelated people with recurrent infections and a significant lack of T cells, specialized white blood cells crucial to the immune system, had the same mutation that hyperactivates Rac2. The study also observed that many of the patient’s neutrophils, cells that capture and ingest invading microorganisms, were enlarged, indicating they were consuming a lot of cellular material.

After reading this study, Denise Montell, who was involved in the 1996 research and is the corresponding author in the current study, wondered whether the T cells’ disappearance was due to innate immune cells with active Rac2 eating them, as had happened with the fruit flies. So, Montell and the other researchers turned their focus to macrophages, the voracious counterpart of the neutrophil. The researchers cultured human macrophages with and without hyperactive Rac2, together with T cells, and found that macrophages with hyperactive Rac consumed more cells, confirming their hypothesis.

Original Submission