Findings from a recently completed genomic analysis published in Nature Medicine indicates that "a high persistent TMB [tumour mutational burden], a biologically relevant measure of tumour foreignness within the overall TMB, represents an 'uneditable' target set for adaptive immune responses and may function as an intrinsic driver of sustained immunologic tumour control that cannot be readily bypassed by neoantigen loss via chromosomal deletions during cancer evolution." Following an extensive evaluation of mutations across 31 tumour types amongst 9,242 patients, along with 8 patient cohorts (total of 524 patients) diagnosed with non-small-cell lung cancer, melanoma, mesothelioma, and head and neck cancer patients, the study team discovered that "mutations in single-copy regions and those present in multiple copies per cell constitute a pTMB...linked with response to immune checkpoint blockade.
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Source mentioned: Niknafs N, Balan A, Cherry C, et al. Persistent mutation burden drives sustained anti-tumor immune responses. Nature Medicine; Published online 26 January 2023. DOI: https://doi.org/10.1038/s41591-022-02163-w
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