Anti-TIF1-γ autoantibodies: warning lights of a tumour autoantigen

Anti-transcription intermediary factor 1 (TIF1)-gamma autoantibodies are robustly linked with cancer-associated DM in adults. This review aims to give an overview of the physiological context of TIF1-gamma and to determine whether there is a pathophysiological link between anti-TIF1-gamma autoantibodies and the occurrence of cancer. Detection of anti-TIF1-gamma autoantibodies has a high sensitivity and specificity for cancer-associated DM in adults and is therefore useful for both diagnosis and cancer risk stratification. The function of the autoantigen, TIF1-gamma, may provide insight into the mechanism behind this association. TIF1-gamma is a ubiquitously present protein involved in various biological pathways, including TGF-beta signalling. In cancer, it can act either as a tumour suppressor or promoter, depending on the cellular context and cancer stage. Evolving data provide pathophysiological insights, linking anti-TIF1-gamma autoantibodies to both the anti-tumour response and to muscle and skin damage. TIF1-gamma expression is increased in muscle and skin tissue of patients with DM. Mutations or loss-of-heterozygosity in TIF1-gamma alleles in malignant tissue may result in the expression of tumour-specific neo-antigens stimulating autoantibody production. The newly formed autoantibodies are hypothesized to cross-react with antigens in muscle and skin, driving the development of DM. Based on the current evidence, anti-TIF1-gamma autoantibodies should be considered warning lights of a potential tumour autoantigen and should alert the physician to the possibility of an underlying cancer.