Do circulating autoantibodies commonly found in healthy individuals reduce cancer risk?

Of the three stages of cancer immunoediting (elimination, equilibrium and escape), the first stage, elimination, where the destruction of early cancer cells prevents them to progress to the subsequent stages of immunoediting and thus prevents cancer development, has been the least studied. Recent laboratory research suggests that autoantibodies (AAbs) play a role in the elimination stage, through recognition of either neoantigens or tumor-associated antigens (TAAs) present on transforming cells. Studies have suggested that natural antibodies (NAbs), which are present from birth, bind to neoantigen-expressing cells, and initiate an immune response that culminates in the destruction of these cells by cytotoxic T cells. It has also been proposed that AAbs developed in response to conditions such as acute infections or inflammatory states bind to TAAs and promote antibody-dependent immune responses. Novel assays permitting a comprehensive assessment of AAb profiles have shown that healthy individuals harbor an abundance of AAbs in their circulation. Little is known about the physiological roles of these common AAbs. Studies have shown that each individual's AAb profile appears specific and is stable over time. We hypothesize that some AAb profiles are associated with a lower risk of developing cancer. This hypothesis could be tested in prospective cohorts that collected blood samples from healthy individuals and followed these individuals for cancer diagnoses, by comparing AAb profiles in participants who did develop cancer during follow-up to those in participants who did not. Identifying AAb profiles associated with cancer risk could lead to improved risk stratification and cancer screening recommendations.