Despite the success of immunotherapy in helping many people with cancer, the majority of patients continue to do so. There is need for continued research.
According to a recent discovery new immune cell soldier might be a good target for immunotherapy, boosting hopes that it might help narrow the gap between those who respond and those who do not.
The new cells, formerly known as killer innate-like Tcells, differ in large ways from the conventional target of many immunotherapies the cytotoxic (aka killer) Tcells. For one, they have no advantage over prolonged activity, such as cytotoxic Tcells. And for another, they can penetrate deeper into tissues where cancer is hiding. These unique attributes make them attractive as a target for immunotherapy.
These killer innate-like Tcells may be targeted or genetically engineered for cancer therapy, according to Ming Li, an immunologist at SKI, and the leading author of the new study. They may be better at reaching and killing solid tumors than conventional Tcells.
Pinning Down What Makes the Cells Distinct
In 2016, the Dr.Lis teamfirst reported the existence of this unusual cell population. At the time, it was clear to his organization that these cells had the capacity to kill cancer cells, but they knew little about where the cells come from or how they work.
For this new experiment, Dr.Li and his colleagues utilized a variety of techniques, including one-cell analysis and CRISPR genome editing, to characterize the cells.
Tcells with killer innate abilities can sabotage the immune checkpoint molecule PD-1, which implies that they do not appear to become exhausted the way typical killer T cells do. This is an attractive feature in a potential immune cell therapy.
Cancer cells appear to recognize different markers, or antigens, on cancer cells. While conventional killer Tcells recognize specific mutated antigens (called neoantigens), the killer innate-like Tcells recognize a much wide range of non-mutated (that is, normal) antigens.
Tcells with less ability to act without antibodies, such as dendritic cells, are not only interested in antigen-presenting individuals, but also are also capable of adopting dangerous immune abilities. In this way, they behave more like innate immune cells that are always well-prepared for attack.
Thirdly, unlike conventional Tcells, they do not recirculate throughout the blood and lymph fluid, making stops in lymph nodes. Rather, they appear to hold directly to tissues throughout the body, where they seek out danger.
All of these are of particular concern as a priority of immunotherapy, according to Dr.Li.
A Unique Fate That Eliminates Autoimmunity and Supresses Cancer
The fact that killer innate-like Tcells recognize unmutated antigens in the body raises the question why these cells do not cause autoimmunity when the immune system attacks normal parts of the body. Dr.Li claims that it is because they are reprogrammed during their development.
Tcells that react strongly to normal antigens are often destroyed off by the body to prevent autoimmune reactions. Despite this fate, the killer innate-like Tcells escape that fate. Instead, their Tcell receptor machinery is tamped down, causing these cells to be harmless to normal cells in the body.
IL-15, a protein that is produced by many cancer cells and that is recognized as an alarmin a danger signal that prods the immune system into action, is significantly enhanced by these individuals. In the same time, the team discovered that if they delete IL-15 from the cancer cells, then the protection provided by the killer innate-like Tcells was eliminated and tumor growth increased.
Because IL-15 isn''t highly produced in healthy tissues, the killer innate-like Tcells would not be spurred into action there, and therefore would not cause unneeded damage.
The Dr.Lis team conducted the majority of their experiments in mice, but they discovered that these killer innate-like Tcells are present in human tumors, including colon cancer tumors from MSK patients. They are particularly interested in the possibility of working with MSK doctors to transact these findings from the lab to the clinic, where they might ultimately assist patients.