Cell Publication: Hypoxia, making T cells more powerful against cancer!
Guide
Recently, in a study published in Cell Reports, a study by the Weizmann Institute of Science showed that T cells of the immune system can destroy cancer cells more effectively after hypoxia.
The plateau training method is a method of exercise training in a low-oxygen environment, which can better exercise the cardiovascular system of athletes and increase the maximum oxygen uptake. However, climbers and endurance athletes are not the only ones who benefit from altitude training. It has been shown that the immune system's anti-cancer cells can also improve their function through this similar method. Recently, in a study published in Cell Reports, a study by the Weizmann Institute of Science showed that T cells of the immune system can destroy cancer cells more effectively after hypoxia.
Using the body's own immune system to fight malignant tumors - that is, cancer immunotherapy has begun to save the lives of cancer patients in the past few years. For example, CAR-T, which was approved by the FDA in the previous period, has been transformed into T cells in vitro by isolating T cells from patients, and is equipped with a “navigation†that specifically recognizes cancer cells. After the body (CAR), the "modified CAR-T cells" are amplified and returned to the patient to exert a specific anticancer effect. To date, this method works best for certain leukemias and lymphomas, but it is not able to fight solid tumors, probably because the microenvironmental oxygen concentration of such tumors is extremely low: 0.5% to 5% of oxygen is dissolved in extracellular fluids— - Below most healthy organs, it is naturally much lower than conventional laboratory incubators (20% oxygen in cell culture fluids).
Let T cells carry out "altitude training method"
Tumor cells do not seem to mind oxygen shortages; even with low oxygen concentrations, they can effectively use glucose as the primary cellular fuel. But this is not the case for T cells, which have difficulty penetrating the tumor and exerting a killing effect. Previous studies have shown that T cells grown in a hypoxic environment can help kill other cells in a laboratory dish, but their true anticancer capabilities have never been tested.
"Destructive T cells are the infantry of cancer immunotherapy. They lock and destroy cancer cells, but they don't always succeed in eliminating malignant tumors," said Professor Guy Shakhar, head of the Wizmann Immunology Department. "We have proven By cultivating these T cells in an oxygen-deficient environment, we can turn them into more effective killers."
In this new study, the researchers asked T cells to perform "altitude training" - they were grown in incubators with oxygen concentrations as low as 1%. The researchers then divided the mice with melanoma into two groups; one group injected hypoxic T cells and the other group injected T cells grown under normal oxygen conditions.
Hypoxic T cells have better anticancer effect
The study found that hypoxic T cells are more effective in fighting cancer. Compared with mice treated with normal T cells, hypoxic T cells treated mice lived longer and their tumor shrinkage was more pronounced. Surprisingly, hypoxic T cells do not penetrate tumors better than normal cells. They are more effective against cancer because they contain a higher level of destructive enzymes, granzyme B, which penetrates and kills cancer cells.
“Just as altitude training improves human endurance, the killer T cells that have undergone 'healthy health' become more tough,†Shakhar said.
If these findings are confirmed in human T cells, it may provide a direct means of enhancing immunotherapy against solid tumors. Shakhar explained: "In cell immunotherapy, T cells need to be removed and cultured in vitro under any circumstances. It is relatively simple to culture under hypoxic stress, but this tiny clinical solution may significantly improve treatment. effect.
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