LAUSR

Simple Summary Rheumatoid factors are autoantibodies that characterize different autoimmune diseases, in particular rheumatoid arthritis, but that can also be found in the sera of the general healthy population. They have been mainly studied in the context of autoimmune diseases, but some evidence have suggested an association between their presence and the predisposition to develop cancer as well as a facilitation of cancer growth and progression in oncologic patients. In this review, for the first time we thus analyze and discuss the possible roles that these autoantibodies can assume in tumor history, from determiners of a heightened susceptibility of developing cancer to drivers of a reduced response to immunotherapies. Abstract The possible interplay between autoimmunity and cancer is a topic that still needs to be deeply explored. Rheumatoid factors are autoantibodies that are able to bind the constant regions (Fc) of immunoglobulins class G (IgGs). In physiological conditions, their production is a transient event aimed at contributing to the elimination of pathogens as well as limiting a redundant immune response by facilitating the clearance of antibodies and immune complexes. Their production can become persistent in case of different chronic infections or diseases, being for instance a fundamental marker for the diagnosis and prognosis of rheumatoid arthritis. Their presence is also associated with aging. Some studies highlighted how elevated levels of rheumatoid factors (RFs) in the blood of patients are correlated with an increased cancer risk, tumor recurrence, and load and with a reduced response to anti-tumor immunotherapies. In line with their physiological roles, RFs showed in different works the ability to impair in vitro anti-cancer immune responses and effector functions, suggesting their potential immunosuppressive activity in the context of tumor immunity. Thus, the aim of this review is to investigate the emerging role of RFs as determiners of cancer faith.