ImmunotherapyConsidered the future of cancer treatment, although there have been many successful cases, immunotherapy still suffers from the problem that the treatment effect varies from individual to individual. But recently scientists have discovered a new type of T cells that have multiple potentials that are more suitable as targets, and may become a powerful assistant for immunotherapy against cancer in the future.
The new type of T cells was first discovered in 2016 by a research team at the Sloan Kettering Institute (SKI), and with subsequent analysis using single-cell analysis and multiple techniques of CRISPR gene editing, the team has also gained a better understanding of how they work. In a new paper in Nature, the SKI team detailed the uniqueness of this “innate killer T cell” (Killer innate-like T cell, ILTCK).
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What’s so special about ILTCK?
First, ILTCK does not express PD-1, so it is not as susceptible to cancer cell-induced T cell exhaustion as CD8+ T cells. Second, unlike traditional T cells, ILTCKs are more tissue-resident and can penetrate deeper into cancer-hidden tissues to search for hidden dangers.
ILTCK also doesn’t rely on antigen-presenting cells like dendritic cells to alert them to the presence of dangerous-looking antigens, features that make them behave more like innate immune cells, always ready to attack.
What’s more, ILTCK also appears to be able to discern between different markers or antigens on cancer cells. It is currently known that CD8+ T cells can only recognize specific neoantigens, while ILTCK cells can recognize a wider range, even unmutated native antigens.
All of these features make ILTCK a potential target for cancer immunotherapy or genetic engineering, says SKI immunologist and study author Ming Li, “They may be more effective than traditional T cells in contacting and killing solid cancer cells. good at.”
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The discovery that ILTCK can identify tumor-native antigens also raises the question: Why don’t these cells cause autoimmune disease? For this problem, the research team believes that the main reason may be related to both the differentiation process of ILTCK and the source of cytotoxicity.
In general, T cells that respond strongly to native antigens are eliminated during development, mainly to avoid triggering autoimmune diseases, but ILTCKs appear to be reprogrammed during development, and their T cell receptors The mechanism is suppressed so that cytotoxicity is not triggered by the mere recognition of the native antigen.
On the other hand, ILTCK seems to be more concerned with the expression of interleukin 15 (IL-15). The team found that once they removed IL-15 from the cancer cells, the protection provided by ILTCK disappeared and the tumors grew. Because many cancer cells express IL-15, the molecule is also considered a danger alarm to stimulate the immune system to function, whereas healthy tissues rarely express IL-15 and naturally do not stimulate ILTCK to function. With dual safeguards, ILTCK can effectively fight cancer cells while being harmless to normal cells in the body.
Although most of the current experiments are carried out in mice, the research team has confirmed that ILTCK cells are also present in human tumors by sampling colon cancer patients. As the research continues, ILTCK may reveal more differences for us. The mechanism of T cells and bring more new perspectives to cancer immunotherapy.
References:
1. Nature, 2022, https://www.nature.com/articles/s41586-022-04632-1
2. https://www.mskcc.org/news/ski-sc
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