Immune cells that fight cancer become exhausted within hours of first encountering tumors – new research

• However, in most patients, cancer cells grow unchecked despite the presence of T cells.
• The current explanation scientists have as to why T cells fail to eliminate cancer cells is because they become “exhausted.” The idea is that T cells initially function well when they first face off against cancer cells, but gradually lose their ability to kill the cancer cells after repeated encounters.
• In our newly published research, we found that T cells become exhausted within hours after encountering cancer cells.

Timing T cell exhaustion

• That would have allowed us to identify the earliest and most critical regulators of T cell dysfunction.
• Instead, we found multiple surprising hallmarks of T cell dysfunction within six to 12 hours after they encountered cancer cells, including thousands of changes in genetic structure and gene expression.
• We analyzed the different regulatory genes and pathways in T cells encountering cancer cells compared to those of T cells encountering infected cells.
• We found that genes associated with inflammation were highly activated in T cells interacting with infected cells but not in T cells interacting with cancer cells.

Boosting T cell killing

• This is because the negative signals cancer cells send out to their surrounding environment induce T cell dysfunction, and a lack of positive signals like inflammation results in a failure to kick T cells into high gear.
• Our team is now exploring strategies to stimulate inflammatory pathways in T cells encountering cancer cells to make them function as though they are encountering an infection.