Cancer in Connective Tissue Disease

Antonio Tonutti^1,2Angela Ceribelli^1,2Elisa Gremese^1,2Serena Colafrancesco^1,2Maria De Santis^1,2*Carlo Selmi^1,2

• ¹Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
• ²Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy

The association between cancer and autoimmunity is well recognized, as represented by the increased incidence of cancer among patients with systemic autoimmune diseases; however, the underlying mechanisms remain only partially understood. On one hand, malignancy may trigger a breakdown of immune tolerance in predisposed individuals, as autoimmune syndromes often emerge shortly after a cancer diagnosis, suggesting that tumor antigens might initiate an autoimmune response. On the other hand, by involving persistent responses and the creation of a pro-inflammatory environment, the chronic immune activation characteristic of autoimmunity may itself promote oncogenesis. The scenario is further complicated by the use of immunosuppressive therapies for autoimmune conditions, which, as seen in transplant immunology, are associated with a higher risk of cancer, although data in rheumatology have not yielded definitive conclusions. Connective tissue diseases include systemic lupus erythematosus, primary Sjögren's syndrome, idiopathic inflammatory myopathies, systemic sclerosis, mixed connective tissue disease, and undifferentiated forms. These conditions have been variably associated with an increased risk of cancer, both at the time of disease onset and in patients with longstanding autoimmune conditions, providing a paradigm for investigating this complex interplay. Despite recent progress, many unmet needs remain and warrant further research efforts.