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The article discusses how renal cell carcinoma (RCC) has unique tumour-specific antigen (TSA) signatures that can trigger cytotoxic immunity, and how small-scale insertions and deletions (INDELs) that result in coding frameshift mutations and activation of human endogenous retroviruses are potential drivers of immunogenicity in RCC. Despite having only an intermediate non-synonymous single nucleotide variation mutational burden, RCC exhibits high cytotoxic T cell reactivity due to high pan-cancer proportion of INDEL frameshift mutations, and coding frameshift INDELs are associated with high immunogenicity. The article also highlights the importance of discovering biomarkers that can inform therapeutic immune checkpoint blockade strategies for RCC.
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