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Cancer drugs known as checkpoint blockade inhibitors have proven effective for some cancer patients. These drugs work by taking the brakes off the body's T cell response, stimulating those immune cells to destroy tumors.
While very powerful in the right settings, immune checkpoint therapies are not effective for all cancer patients. This work makes clear the role of genetic heterogeneity in cancer in determining the effectiveness of these treatments." Because these tumors have so many mutated proteins, they are believed to be good candidates for immunotherapy treatment, as they offer a plethora of potential targets for T cells to attack. Over the past few years, the FDA has approved a checkpoint blockade inhibitor called pembrolizumab, which activates T cells by blocking a protein called PD-1, to treat several types of tumors that have a high TMB.
Related StoriesThe researchers discovered that this lack of response appears to be the result of a phenomenon known as intratumoral heterogeneity. This means that, while the tumors have many mutations, each cell in the tumor tends to have different mutations than most of the other cells. As a result, each individual cancer mutation is "subclonal," meaning that it is expressed in a minority of cells.
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