Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

Abstract

Auto-antibodies are classically associated with autoimmune diseases, where they are an integral part of diagnostic panels. However, recent evidence is accumulating on the presence of auto-antibodies against single or selected panels of auto-antigens in many types of cancer. Auto-antibodies might initially represent an epiphenomenon derived from the inflammatory environment induced by the tumor. However, their effect on tumor evolution can be crucial, as is discussed in this paper. It has been demonstrated that some of these auto-antibodies can be used for early detection and cancer staging, as well as for monitoring of cancer regression during treatment and follow up. Interestingly, certain auto-antibodies were found to promote cancer progression and metastasis, while others contribute to the body’s defense against it. Moreover, auto-antibodies are of a polyclonal nature, which means that often several antibodies are involved in the response to a single tumor antigen. Dissection of these antibody specificities is now possible, allowing their identification at the genetic, structural, and epitope levels. In this review, we report the evidence available on the presence of auto-antibodies in the main cancer types and discuss some of the open issues that still need to be addressed by the research community.

Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity

“…After surgical resection and chemoradiotherapy for the malignancy, we observed that the ANA of the patient became negative and there was a significant decrease in LA. This reminded us to consider a positive result of ANA and LA in our case dialectically because studies have shown that ANA and LA are associated with malignancy (30)(31)(32)(33).…”

The Autoantibodies against Tumor-Associated Antigens as Potential Blood-Based Biomarkers in Thyroid Neoplasia: Rationales, Opportunities and Challenges

“…As compared with the traditional tumor markers and the diagnostic targets of the liquid biopsy (e.g., circulating tumor cells, cell-free tumor DNA/RNA, etc.) (reviewed in [ 20 , 21 ]), the TAA-AAbs are characterized by a set of unique properties rendering them particularly suitable for some of the diagnostic applications but significantly limiting their use in others [ 10 , 11 , 12 ].…”

“…Finally, the autoantibodies against bona fide TAAs usually demonstrate very high diagnostic specificity (DSp) in the detection of malignancy (typically 90–95% or higher), whereas their diagnostic sensitivity (DSn) is usually low-to-moderate (typically 10–25% for a single TAA-AAb) [ 12 ]. It implicates the TAA-AAbs as the perfect candidates for the «rule in» tests, whereas their use for «rule out» diagnostics usually requires a combination of TAA-AAbs against several TAAs in a single diagnostic panel, also referred to as autoantibody signature (such as in EarlyCDT ® -Lung test, see Section 3.2 ), concurrent use of TAA-AAbs with other types of biomarkers or diagnostic approaches, or use of the benign tumor-associated TAA-AAbs that disappear upon progression to malignancy and thus may be used for implicit ruling out of malignancy via confident ruling in the benign nature of a tumor (see Section 6 ).…”

“…One particular type of tumor markers that was extensively implicated in human cancer but remains understudied in thyroid neoplasia is circulating autoantibodies (AAbs) against tumor-associated antigens (TAAs) (see Section 2 , reviewed in [ 10 , 11 , 12 ]). A variety of experimental techniques for a systematic survey of TAAs’ and TAA-AAbs’ repertoires have been successfully implemented for the identification of a large number of TAAs; yet, the technical aspects of TAAs’ identification are out of scope of the present review, and I refer readers to recent comprehensive reviews in the field [ 13 , 14 , 15 ].…”

TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

“…Autoantibodies against nuclear and cytoplasmic autoantigens have been detected in cancer patients, with possible causal mechanisms including autoantigen overexpression from tumour cells and autoantigen release following chemotherapy-induced cell death ( 132 ). Recently, anti-TRIM21 antibodies have been detected in patients with ovarian cancer, the presence of which correlated with better patient survival.…”