Fight Aging!

Researchers here identify distinctive markers for a population of regulatory T cells that act to protect at least some types of tumor tissue from the rest of the immune system. Cancers subvert the immune system in a range of ways, making it blind to cancer cells, and even making immune cells assist in the growth of the cancer. In principle destroying these protective, subverted immune cells could produce a renewed attack on a tumor, or at the very least make it more vulnerable to present therapies, particularly those that encourage immune cells to attack cancer cells.

Some types of T cells work to calm their over-active brethren. Known as regulatory T cells, or T-regs, they typically tamp down inflammation, quieting that mob and thereby protecting nearby healthy tissues. In tumor tissue, researchers found a different flavor of T-regs. These immune-suppressing cells, swarming in tumor-environment specimens, were different from T-regs found elsewhere in the body. Their cell surfaces are marked by two distinct protein receptors. These specially marked T-regs were particularly good at tamping down inflammation, expanding in number and protecting the tumor cells from attack by other types of T cells.

To a casual observer, the T-regs from the tumor samples would look no different from those found elsewhere in the body. But the team used new techniques that allow scientists to identify characteristics of tens of thousands of individual cells in a sample, and advanced computing methods to sift through data. It allowed them to spot two types of receptor proteins on the surfaces of T-regs collected from the tumor. The telltale proteins have names only a scientist could love: IL-1R1 and ICOS. "What makes these cells unique is that they express both those proteins. You just don't see that co-expression on other T-reg cells."

One reason this pair of proteins may have been overlooked by researchers previously is that they occur in human T-regs, not in those of mice. Much of laboratory work in immunology relies on mouse models of the immune response, but this study focused on human tissues, taken from patients who either had cancer or non-cancerous lesions. Researchers hypothesize that these tumor-resident T-regs have been tricked by cancer into working for the wrong team. Surrounded by T cells searching for cancer cells to destroy, the tumors acquired an ability to either attract or generate a blanket of these ICOS/IL-1R1-bearing T-regs. Exactly how they did so is not clear, but their impact is to build up an immunosuppressive environment, protecting the tumor from ordinary T cells doing their jobs.

Link: https://www.fredhutch.org/en/news/center-news/2022/05/regulatory-t-cells-solid-tumors.html