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Author: Sophia
Introduction: CD8 T cells are crucial for eliminating cancer cells. Factors in the tumor microenvironment can drive these cells into a less functional state known as failure. The most terminally exhausted T (tT+ex) cells are resistant to checkpoint blockade immunotherapy , which may limit the efficacy of immunotherapy.
When T cells, the primary cancer killers of the immune system , work overtime to fight tumors, they enter a state of exhaustion and no longer function properly. Researchers from the University of Pittsburgh and UPMC Hillman Cancer Center published a research paper in "Nature Immunology" on December 21, reporting that the low-oxygen environment of tumors can prompt these exhausted T cells to change loyalty, thereby suppressing the immune system rather than fighting the cancer.
https://www.nature.com/articles/s41590-022-01379-9
What are exhausted T cells
01
Exhausted T cells are the warriors of our immune system, and they are constantly fighting cancer. Our immune system uses T cells to find and kill abnormal cells, such as those that are cancerous or infected by the virus , and they are built to continue fighting until every abnormal cell has been eliminated. But in diseases like cancer, where cancer cells keep pace with the immune system, the cells may not work properly and abnormal cells persist. As T cells keep fighting these cancer cells, their job gets worse and worse.
Exhausted T cells are an adaptive response to too many "signals." These signals can come from pathological sources, such as cancer or viruses, but they also appear in healthy tissue, so we find that in autoimmune diseases , the immune system attacks the host inappropriately, and in the placenta, the mother's immune system adapts to the growing fetus. In these cases, T cell exhaustion is a good thing: it helps control unnecessary damage by activating T cells.
Research finds
02
Because exhausted T cells can no longer kill cancer cells, they have become targets for cancer immunotherapy. If we could revive them, they would be effective at killing cancer cells again. Our research found that when exhausted T cells enter tumors, they don't just weaken their own functions, they actually change their surrounding environment and actively shut down other nearby cells. In other words, exhausted T cells not only fail to work for us, they are actively working against us.
The idea that exhausted T cells work against us in cancer opens up new avenues for immunotherapy, such as developing treatments that target the pathways responsible for switching, or designing better T cells for cell-based therapies. While the immunotherapy field has rightly focused on correcting the loss of anti-cancer function of T cells, our efforts suggest that we should also study the potential novel behaviors acquired by these cells.
Exhaustion cells have many similarities to regulatory cells, which are cells that help the immune system control itself to prevent autoimmune diseases. We found that exhausted cells mimic regulatory cells by suppressing the immune system. Beyond this, we were surprised to find that the immunosuppressive function of exhausted T cells is related to the environment in which they are studied. In short, we found that more aggressive tumors tended to have more immunosuppressive exhausted T cells, whereas slower growing tumors had functionally exhausted T cells but not suppressive .
Development Prospects
03
Researchers are currently conducting several clinical trials at Pittsburgh using these environment-modifying drugs to treat cancer patients. The next big question will be whether we can reverse the immunosuppressive properties of T-cell depletion in these patients. We are also interested in developing drugs that directly target the suppressive properties of patients' T cells.In addition to cancer, exhausted cells are also present in chronic infections such as hepatitis and HIV, autoimmune diseases such as lupus and type 1 diabetes, and in the gut. Discovering the role of these cells and their inhibitory properties in other settings will be a new direction for this research.
Reference:
https://medicalxpress.com/news/2022-12-turncoat-cells-exhausted-cancer-fighting-sides.html
https://www.nature.com/articles/s41590-022-01379-9
Note: This article is intended to introduce medical research progress and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital.
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