How a cancer fighter becomes a tumor co-conspirator

T cells are frequently viewed as crucial immune system protectors who work on the front lines of the battle against pathogens. Therefore, it is simple to assume that when T cells are found in large numbers in colorectal tumors, they are "one of us" and valiantly battling cancer cells to stop tumor growth.

Indeed, there is some research evidence that has shown that a class of T cells residing in the intestine can prevent tumor formation. They are called ?? T cells because the T cell receptors on their surface for antigen recognition are composed of? and? chains, as opposed to conventional T cells that are composed of? and? chains. Because?? T cells are often present in some cancer-bearing tissues and are able to respond to the stress signals that almost all cancer cells produce, some even believe that?? T cells belong to a class of T cells that were born to fight cancer cells.

Surprisingly, though, it is these specific anti-tumor T cells that have the potential to "defect" and join forces with the tumor. This new discovery was recently made public by a research team from Rockefeller University in the prestigious academic journal Science.

The study reveals that?? T cells actually have two faces—by changing the usage of the T cell receptor gene V??, and when the "turning traitor" occurs is related to the progression of cancer development.?? T cells that reside in the intestine do prevent tumors, but once a tumor forms, the intestinal?? T cell population changes, enters the tumor, and promotes tumor growth.

Using a mouse colorectal cancer model, the researchers isolated and extracted?? T cells from the intestines of animals with early and advanced stages of cancer for analysis. The findings revealed significant molecular variations between the two, including various T cell receptors.

Dr. Bernardo Reis, first author of the paper, said that?? T cells have completely changed.

Of particular interest is the production of interleukin-17 (IL-17) by?? T cells that enter the tumor. This pro-inflammatory cytokine typically causes an inflammatory reaction following an infection. Additionally, T cells' production of IL-17 in the tumor microenvironment indicates that they are likely to promote tumor growth and aid in the concealment of tumors from other immune system components.

To further demonstrate that the role of?? T cells had shifted, the team used CRISPR gene editing to selectively alter the T cell receptors of these cells, which then jumped between "anti-cancer" and "pro-cancer". "When we removed the original?? T cells, the mouse got worse, and when we eliminated the infiltrating?? T cells, the tumors shrank." Dr. Reis said.

The team further validated the findings from mice in human colorectal cancer samples. After analyzing and comparing the?? T cells in the tumor tissue and the surrounding tissues, they observed similar differences—the cells inside the tumor resembled the?? T cells that had "defected" in the advanced stages in the mouse model, while the cells outside the tumor appeared to be the same?? T cells that were still fighting cancer in the first place. "It's very much a struggle between two groups of cells, with the regular cells trying to limit the tumor and the cells going inside promoting tumor growth."

The discovery of the transformation of?? T cells from intestinal allies to tumor accomplices has also prompted researchers to subsequently look for new opportunities to treat cancer. For example, whether normal?? T cells could be regulated to suppress tumors and prevent renegade?? T cells from dominating. Even more, the researchers suggested that they could take advantage of?? T cells that infiltrate tumors. Dr. Reis added, "Maybe one day we can turn?? T cells into Trojan horse viruses and have them act as anti-cancer cells in the tumor microenvironment."

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