An international team of researchers from Israel, the US, and China has developed a genetic method to reprogramme a type of immune cell, turning them from cancer promoters to inhibitors.
The team, led by Israel`s Weizmann Institute of Science, focused on macrophages — a type of immune cell that can induce immune responses. But in many cancers, macrophages become allies that protect the tumour, help it grow, and even aid in spreading it to other tissues, Xinhua news agency reported.
Using advanced gene-editing tools and artificial intelligence, the researchers analysed human tumour samples and identified 120 genes potentially responsible for the transformation.
“Macrophages are highly versatile cells, sort of a ‘Swiss knife’ of the immune system, capable of activating multiple types of functions for different tasks and in different situations,” said Prof. Ido Amit, a faculty member of Weizmann’s Systems Immunology Department.
These cells can potentially be highly effective cancer eradicators that can perform multiple antitumor functions, such as promoting anticancer inflammation or alerting the rest of the immune system to the dangers posed by tumour cells. That’s precisely the reason most solid cancers need to convert macrophages to their side to develop.
“By doing that, the tumours protect themselves from the macrophages’ ‘nasty’ side, and also turn on macrophage functions that help them grow, such as suppressing the activity of other immune cell types and encouraging blood vessel growth for supplying oxygen to the tumour,” Amit added.
Through CRISPR-Cas9 gene editing and single-cell analysis, they zeroed in on a gene named Zeb2.
The researchers found that Zeb2 acts as a master switch. When the gene is active, it turns macrophages into cancer supporters. When silenced, macrophages revert to their natural, cancer-fighting role.
Further studies showed that Zeb2 alters the epigenome — the genome`s control centre — unlocking genes that help cancer and shutting down those that fight it.
The team designed a DNA molecule that delivers a gene-silencing agent directly into macrophages.
In mice with bladder cancer, injecting the molecule into the tumour successfully reprogrammed the macrophages. The tumours got significantly smaller.
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