T Cell Response Varies Widely Between Individuals and is Important in Suppressing Cancer

Different individuals can have very different degrees of vulnerability to any given cancer, depending on how aggressively the adaptive immune system responds to that cancer. Researchers here explore some of the mechanisms in T cells responsible for varying vulnerability to cancers - it many cases it is blind luck as to whether or not the T cell population is capable of immediately recognizing a specific lineage of cancerous cells. That T cells are so important to the cancer response may explain why the age-related decline of the thymus correlates very well with rising cancer risk. The thymus is where thymocytes mature into T cells, but the organ atrophies with age, causing a progressive reduction in the number of new T cells entering the immune system. Those missing cells lower the odds of the immune system being able to recognize a specific cancer cell lineage as a threat.

Researchers have established a mouse model to help them understand why some hosts' immune systems reject tumors easily, while others have a harder time doing so. The scientists started the research by transplanting tumors into genetically identical mice. Theoretically, their response to the cancer would be identical, but it turned out that 25% of the mice spontaneously rejected the tumor. The researchers started looking more closely at both the mice and the tumor cells to try to understand what was causing the mice to kill the cancer on their own.

What they discovered is that it all depended on the types of the immune cells known as CD8 T cells that were present in the mouse. Even identical twins have different T cells due to the random DNA recombination event generating these T cells, so the genetically identical mice had different arrays of the T cells as well. The mice's response to cancer depended on how their specific T cells matched up with the set of mutated proteins known as neoantigens that were present in the tumor they were fighting.

"Each of your T cells has a different receptor, and each T cell will be specific to a neoantigen. If you have T cells that are specific to all of them or majority of them, you're going to be able to get rid of your tumor and have a good anti-tumor immune response." The researchers showed that the mice that spontaneously rejected tumors had vastly different T cell receptors from those that succumbed to tumor development.

Link: https://news.cuanschutz.edu/cancer-center/role-of-t-cells-in-fighting-cancer


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