New cancer treatments may wake up the immune system

Immunotherapy is a promising strategy to treat cancer.

Their new method involves removing tumor cells from the body, treating them with chemotherapy drugs, and then putting them back into the tumor

"When you create cells with damaged DNA but not killed, under certain conditions, these cells will survive, and the injured cells will send a signal to wake up the immune system," David H.

In the study of mice, the researchers found that this treatment can completely eliminate tumors in nearly half of the mice

Yafei and Underwood-Prescott Professor Darrell Irwin who served in the Department of Bioengineering and Materials Science and Engineering at the Massachusetts Institute of Technology, as well as the deputy director of the Koch Institute, are the senior authors of the study.

T cell activation

One class of drugs currently used in cancer immunotherapy is checkpoint blockade inhibitors, which can stop T cells that are "exhausted" and unable to attack tumors

Yaffe and his colleagues began to try to improve the performance of these drugs by combining these drugs with cytotoxic chemotherapy drugs, hoping that these chemotherapy can help stimulate the immune system to kill tumor cells

Some clinical trials of combining chemotherapy and immunotherapy drugs are ongoing, but so far little is known about the best combination of these two treatments

The MIT research team first used several different doses of chemotherapy drugs to treat cancer cells

The researchers later realized why this happened: It was not the dead tumor cells that stimulated the immune system; instead, the key factor was those cells that were damaged by chemotherapy but were still alive

Yaffe said: "This describes a new concept of immunogenic cell damage rather than immunogenic cell death in cancer treatment

The drugs that work best under this method are those that cause DNA damage

Yafei said: "Our findings are fully in line with the concept that'danger signals' in cells can talk to the immune system.

Tumor elimination

In a study of mice with melanoma and breast tumors, the researchers found that this therapy completely eliminated 40% of the tumors in the mice

The researchers also tried to inject DNA-destroying drugs directly into the tumor instead of treating the cells in vitro, but they found that this was ineffective, because chemotherapy drugs also harm T cells and other immune cells near the tumor

Yafei said: "You must provide some immunostimulants, but at the same time you must also release the original barriers on the immune cells

Yaffe hopes to test this method on patients whose tumors do not respond to immunotherapy, but more research is needed first to determine which drugs and dosages are most effective for different types of tumors
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Researchers are further studying the details of how damaged tumor cells stimulate such a strong T cell response
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