Abstract
A link between autoimmune responses and cancer via autoantibodies was first described in the 1950s. Since, autoantibodies have been studied for their potential use as cancer biomarkers, however the exact causes of their production remain to be elucidated. This review summarizes current theories of the causes of autoantibody production in cancer, namely: 1) defects in tolerance and inflammation, 2) changes in protein expression levels, 3) altered protein structure, and 4) cellular death mechanisms. We also highlight the need for further research into this field to improve our understanding of autoantibodies as biomarkers for cancer development and progression.
Highlights
The production of autoantibodies (AAbs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells [1]
It may be possible that the reduced production of Tregs or similar Treg downregulatory mechanisms exist in human melanoma or other cancers, rendering Treg/T cell receptor (TCR) binding ineffective and promoting autoantibody production in some cancer patients, with potential beneficial outcomes
An induction of inflammation in the tumor microenvironment has been suggested to facilitate the release of intracellular antigens resulting in abnormal exposure of autologous antigens to the immune system, which may provide an explanation for the vast number of autoantibodies produced against intracellular antigens in cancer patients [28]
Summary
The production of autoantibodies (AAbs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells [1]. Over the last few decades, AAbs have become of particular interest as cancer biomarkers as they can be extracted from serum via minimally invasive blood collection They exhibit increased levels in very early cancer stages [3] and are observed in patients with several carcinomas, including breast [4], lung [5], gastrointestinal [3], ovarian [6], and prostate [7]. Maintenance of clonal anergy is problematic as it requires constant receptor occupancy and signalling, and is reversed by dissociation of the corresponding self-antigen, resulting in anergic self-reactive B cells regaining responsiveness and potentially leading to the production of autoantibodies [27]. Exposure of some autologous nuclear antigens to the immune system, i.e., following tumor cell lysis, may result in the production of autoantibodies [28]
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