Researchers discover new ways to activate cells that kill cancer

If the situation is right, the body’s T cells should detect and kill the cancer cells. However, most cancer patients have been found to be unable to do so once they enter the environment surrounding the tumor.

This study was published in the “Immunity Journal”.

Scientists are now trying to find ways to help treat patients by jump-starting these matte T cells. Much of the research in this area, known as cancer immunotherapy, focuses on finding ways to directly stimulate these T cells. Researchers at MIT have discovered new ways to indirectly activate these T cells by mobilizing a population of helper immune cells called dendritic cells.

In a new study, researchers identified a specific subset of dendritic cells that had their own way of activating T cells. These dendritic cells can hide in tumor proteins and impersonate cancer cells to provoke a strong T-cell response.

“We knew that dendritic cells were very important for the antitumor immune response, but we didn’t really know what the optimal dendritic cell response to the tumor was,” Howard S. and Linda said. B. Stern Career Development Professor Stephanis Planger said. A member of MIT and the Koch Institute for Integrative Cancer Research at MIT.

The results suggest that finding a way to stimulate a particular population of dendritic cells may help increase the effectiveness of cancer immunotherapy, she said. In a mouse study, researchers showed that stimulating these dendritic cells slowed the growth of melanoma and colon tumors.

Natural regression

When a tumor begins to form, it produces a cancerous protein that T cells recognize as a foreign body. This may allow the tumor to be eliminated before the T cells become very large. In other cases, the tumor can secrete chemical signals that inactivate T cells, allowing the tumor to continue to grow unsuppressed.

Dendritic cells are known to help activate T cells that fight tumors, but there are many different subtypes of dendritic cells, and their individual role in T cell activation is complete. Not characterized. In this study, the MIT team wanted to investigate what types of dendritic cells were involved in the T cell response to successfully eliminate tumors.

To do that, they found a tumor cell line in a type of muscle tumor that has been shown to spontaneously regress in mice. According to Spranger, such cell lines are difficult to find if they are unable to form tumors, as researchers usually do not maintain them.

By studying mice, they compared the tumors produced by their degenerative cell lines to the types of colon cancer that form tumors that grow after being transplanted into the body. Researchers have found that in developing tumors, the T cell response is quickly depleted, and in regressing tumors, T cells continue to function.

Next, the researchers analyzed the dendritic cell populations present in each of these tumors. One of the main functions of dendritic cells is to take up debris from dying cells, such as cancer cells and cells infected with pathogens, and present protein fragments to T cells to warn of infections and tumors.

The most well-known type of dendritic cell required for anti-tumor immunity is DC1 cell, which interacts with T cells that can eliminate cancer cells. However, researchers have found that DC1 cells are not required for tumor regression. Instead, single-cell RNA sequencing techniques were used to identify previously unknown activation states of DC2 cells. It is a different type of dendritic cell that promotes T cell activation in degenerative tumors.

Instead of ingesting cell debris, the MIT team discovered that these dendritic cells swipe from tumor cells a protein called the MHC complex and display them on their surface. When T cells encountered these dendritic cells disguised as tumor cells, they were strongly activated and began to kill the tumor cells.

This particular population of dendritic cells appeared to be activated by type 1 interferon, a signaling molecule normally produced by cells in response to viral infections. Researchers have found small populations of these dendritic cells in advanced colon and melanoma tumors, but they have not been properly activated. However, when those tumors were treated with interferon, the dendritic cells began to stimulate T cells to attack the tumor cells.

Target therapy

Although some types of interferon have been used to help treat cancer, systemic administration can cause widespread side effects. The results of this study suggest that it may be beneficial to deliver interferon in a very targeted manner to tumor cells, or to use drugs that induce tumor cells to produce type I interferon. Suggested, Spranger said.

Researchers are currently planning to investigate how much type I interferon is needed to generate a strong T cell response. Most tumor cells produced small amounts of type I interferon, but not enough to activate the dendritic cell population that activates T cells. On the other hand, too much interferon can cause cell toxicity.

“Our immune system is wired to react very dramatically to the subtle differences in type I interferon, which is interesting from an immunological point of view,” Spranger said.