through the high number of mutations found within these cancer cells. Such mutations can serve as cues that enable the immune system to identify and combat the tumor. In the context of ICB, weaker mutation signals lead to a diminished response to treatment because the immune system has a harder time finding and recognizing the cancer cells., highlight the pivotal role played in this process by intratumoral heterogeneity.
"One way to picture this is to imagine a crowd, where each person is holding a yellow flashlight," explained Isidro Cortes-Ciriano, Research Group Leader at EMBL-EBI. have different mutations, the signal is harder to make out and the immune system is not triggered, so ICB doesn't work."ICB has shown remarkable efficacy in tumors with a high number of mutations, In particular, this applies to tumors with clonal neoantigens. Clonal neoantigens occur when identical mutations are present across all cells of a tumor. Despite this, less than half of MMRd tumors show long-lasting response to ICB, posing a significant challenge in optimizing treatment.