Science Signaling: In vitro chemotherapy "kills" cancer cells, combined with immunotherapy to eliminate tumors without recurrence

In recent years, the rapid development of tumor immunotherapy has brought new hope for mankind to completely overcome cancer, but it is only effective for a small number of cancers
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Immunotherapy uses the body's own immune system to attack cancer, but most tumors create a highly immunosuppressive environment that inactivates T cells

On October 19, 2021, researchers from the Massachusetts Institute of Technology published a research paper entitled "The injury response to DNA damage in live tumor cells promotes antitumor immunity" in the journal " Science Signaling "
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Researchers have discovered a new way to treat tumors, using damaged tumor cells to wake up the immune system to attack tumors.
In a mouse model, this therapy can completely eliminate tumors in nearly half of the mice
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One class of drugs currently used for cancer immunotherapy is checkpoint blocking inhibitors, which can stop T cells that have been exhausted and cannot attack the tumor
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These drugs have been successful in treating several types of cancer, but have no effect on many other types of cancer

In this study, the researchers tried to improve their performance by combining these drugs with cytotoxic chemotherapy drugs, hoping that chemotherapy could help stimulate the immune system to kill tumor cells
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The researchers first used several different chemotherapeutics to treat isolated cancer cells in different doses
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After 24 hours, the researchers added dendritic cells to each dish, and T cells after 24 hours

Surprisingly, the researchers found that most chemotherapeutic drugs did not have much effect, and those drugs that helped the treatment seemed to work best at low doses without killing many cells
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Therefore, the researchers said, it is not the dead tumor cells that stimulate the immune system.
On the contrary, the key factor is the cancer cells that are injured by chemotherapy but are still alive
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Cultured in vitro, injected into the body, combined with systemic immune checkpoint blockade to activate the immune system

In addition, the researchers found that the most effective drugs are those that can cause DNA damage, because when tumor cells undergo DNA damage, it activates cellular pathways that respond to stress
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These pathways send out distress signals and stimulate T cells to act quickly, not only destroying injured cells, but also destroying any nearby tumor cells

DNA-damaged tumor cells mediate T cell response

In mouse models with melanoma and breast tumors, this therapy completely eliminated tumors in 40% of mice
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Not only that, when the researchers injected cancer cells into these mice a few months later, the mice’s T cells recognized and eliminated them before they formed new tumors, and no longer recurred
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Researchers have also tried to inject DNA-damaging drugs directly into tumors in the body, rather than cells outside the body, but they found that this is not effective because chemotherapy drugs can also damage T cells and other immune cells near the tumor
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In addition, injecting damaged cells without checkpoint blocking inhibitors has no effect

In short, the study describes a new cancer treatment method that uses chemotherapeutic drugs plus immunotherapy to completely eliminate tumors, and has long-term anti- tumor immune memory without recurrence
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Finally, the researchers hope to test this method in patients whose tumors do not respond to immunotherapy, but first, more research is needed to determine which drugs and dosages are most beneficial for different types of tumors
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Researchers are further studying the details of how injured tumor cells stimulate such a strong T cell response

Original source:

GANAPATHY SRIRAM LAUREN E.