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Scientists Discover New Innate T Cells With Potential For Cancer Immunotherapy

Researchers at the Sloan Kettering Institute have recently discovered a new immune cell "solider", which could be used well in immunotherapy, thus offering help to people who do not respond well to the treatment.

This treatment is expected to bridge the gap between people who do not respond to the treatment and those who respond positively.

The new cells, which the scientists have named killer innate-like T cells differ in many ways from the usual target of many immunotherapies i.e, the cytotoxic or killer T cells. Firstly, they do not get tired from extended activity like the normal cytotoxic T cells do. And two, they can enter more deeply into tissues, where the cancer is hiding. These unique attributes make them helpful as a target for immunotherapy.

Commenting on the findings of the study, Ming Li, an immunologist in SKI and the lead author of the new study, said, "We think these killer innate-like T cells could be targeted or genetically engineered for cancer therapy. They may be better at reaching and killing solid tumors than conventional T cells."

Dr. Li's team first came to know of this unusual cell population in 2016. From then on it was clear to the team that these cells had the power to kill cancer cells, but very little was known about how they function and what are their characteristics.
For this new study, Dr. Li and his team used a variety of techniques, including single-cell analysis and CRISPR genome editing, to further understand the cells.

They made several startling discoveries. For one, killer innate-like T cells don't make the immune checkpoint molecule PD-1 and, as a result, do not appear to become exhausted the way typical killer T cells do. This could be important for potential immune cell therapy.

The cells also appear to recognize different markers, or antigens, on cancer cells. Whereas conventional killer T cells recognize specific mutated antigens or neoantigens, the killer innate-like T cells recognize a much broader range of non-mutated or normal antigens.

The fact that killer innate-like T cells recognize unmutated antigens in the body raises the question as to why these cells don't cause autoimmunity i.e when the immune system attacks normal parts of the body. Dr Li says it's because they get reprogrammed during their development.

Typically, developing T cells that react strongly to normal antigens are proactively killed off by the body to prevent autoimmune reactions. But the killer innate-like T cells escape that fate. Instead, their T cell receptor machinery gets tamped down, rendering these cells harmless to normal cells in the body.

At the same time, they become much more sensitive to a molecule called IL-15, which is produced by many cancer cells and is recognized as an "alarmin", i.e, a danger signal that prods the immune system into action. The team found that if they delete IL-15 from cancer cells, then the protection provided by the killer innate-like T cells was eliminated and tumor growth increased.

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