Spontaneous autoantibody responses against tumor-associated antigens have been detected in all types of cancer
analyzed so far. Recent studies have shown that cancer-associated autoantibodies can be found in the serum of patients
even several years before the clinical diagnosis. Furthermore, they may at least partially reflect the antigenic profile of
cancer and the balance of immune cell subsets in the tumor microenvironment. Therefore, cancer associatedautoantibodies
represent attractive biomarkers for the development of non-invasive serological tests for the diagnosis or
early detection of cancer, prognosis of survival and prediction of the clinical benefit of immunotherapy. Still, the frequency
of responses against each particular antigen is generally low and the autoantibody repertoire is highly heterogeneous
and overlapping with that elicited by viral infections and autoimmune disorders, hence precluding the clinical use of
single autoantibody biomarkers. This can, however, be overcome by analyzing the autoantibody responses to multiple antigens
simultaneously. In this review, we discuss the diagnostic relevance of the recently identified cancer-associated
autoantibody signatures and the challenges in the development of clinically applicable biomarker assays. In addition, the
putative functional role and the significance of IgG subclasses in the anti-tumor immune response and their prognostic
value are discussed.
Keywords: Autoantibodies, B cells, biomarkers, early detection of cancer, proteomics, tumor antigens.
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