Review: Cancer‐Induced Autoimmunity in the Rheumatic Diseases

Tantalizing connections between autoimmune rheumatic diseases and cancer have become increasingly evident over the past several decades. These connections are complex, with different relationships in frequency, timing and types of cancers observed in different diseases or disease subgroups. Several recent advances from disparate fields have begun to illuminate the dynamic and bidirectional interactions occurring at the cancer-immune system interface which may be relevant to understanding the origins of autoimmunity (1). These interactions include the existence of potent anti-cancer immune responses which limit tumor growth, as well as multiple immune and inflammatory pathways that can contribute to tumor growth and robustness. The striking ability of immune checkpoint inhibitors to reveal powerful anti-cancer immune responses in patients with cancer highlight that natural immune responses to cancers exist, and may regulate the emergence of cancer (2). Recent data in systemic sclerosis (SSc, scleroderma) patients suggests that, in some cases, autoimmunity may be initiated by autoantigen mutation in that patient’s cancer (3, 4). Interestingly, there exist patients with the same form of scleroderma and an identical autoimmune response who do not have a detectable cancer, raising the possibility that in these patients, the disease mechanism is the same except that the anti-tumor immune response has successfully eliminated the cancer. Similar striking associations with cancer are also apparent in other rheumatic phenotypes, particularly dermatomyositis (DM). The autoimmune rheumatic diseases therefore provide an exceptional opportunity to study cancer-immune interactions, and interrogate the mechanisms of the autoimmune rheumatic diseases, as well as the natural immune response to cancers in humans.