Autoantibody Diversity Is Associated with Reduced Cancer Emergence in DM

Dermatomyositis (DM) and the subsequent development of cancer exhibits temporal clustering, typically occurring within 3 years of diagnosis. This phenomenon has been found to be more likely to occur in patients who have autoantibodies against transcriptional intermediary factor 1-γ (TIF1-γ). However, not all patients who have these autoantibodies are diagnosed with cancer, with one explanation being that effective antitumor responses in these patients prevent their cancers from emerging. Therefore, Fiorentino and colleagues investigated the specificity of additional autoantibodies in patients with DM who display anti–TIF1-γ antibodies but did not develop cancer. Ten specific autoantibodies were defined, with four being found with a frequency greater than 6.5%. The most frequently occurring autoantibody in two independent cohorts was against cell division cycle and apoptosis regulator protein 1 (CCAR1), which was found to occur in 32% of patients, with these anti-CCAR1 antibodies being rarely detected in patients negative for anti–TIF1-γ antibodies. The presence of anti-CCAR1 antibodies was negatively associated with cancer emergence within 3 years of DM onset, with no association between these autoantibodies and the development of any specific cancer type being observed. Cancers did eventually arise in a sufficient number of anti-CCAR1–positive cases; however, they were diagnosed later after DM diagnosis (4.3 versus 0.85 years) and were more localized and at a lower stage than cancers in anti–TIF1-γ antibody–positive patients alone. Further analysis into additional antibodies and cancer emergence indicated that patients with DM who were cancer-negative displayed a larger number of prominent antibodies with an increasing number of targets moving from short-interval cancer to long-interval to no cancer, indicating a dose–response inverse relationship between cancer emergence and the number of additional antibody specificities. This study suggests the association of antigen-specific immune response, such as those against CCAR1, with protection from cancer emergence after DM diagnosis and provides further understanding of the mechanisms behind natural immune regulation of cancer.

Fiorentino DF, Mecoli CA, Rosen MC, Chung LS, Christopher-Stine L, Rosen A, et al. Immune responses to CCAR1 and other dermatomyositis autoantigens are associated with attenuated cancer emergence. J Clin Invest 2022;132:e150201.

Note:Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.