Small-cell lung cancer-associated autoantibodies: potential applications to cancer diagnosis, early detection, and therapy

Abstract

Small-cell lung cancer (SCLC) is the most aggressive lung cancer subtype and lacks effective early detection methods and therapies. A number of rare paraneoplastic neurologic autoimmune diseases are strongly associated with SCLC. Most patients with such paraneoplastic syndromes harbor high titers of antibodies against neuronal proteins that are abnormally expressed in SCLC tumors. These autoantibodies may cross-react with the nervous system, possibly contributing to autoimmune disease development. Importantly, similar antibodies are present in many SCLC patients without autoimmune disease, albeit at lower titers. The timing of autoantibody development relative to cancer and the nature of the immune trigger remain to be elucidated. Here we review what is currently known about SCLC-associated autoantibodies, and describe a recently developed mouse model system of SCLC that appears to lend itself well to the study of the SCLC-associated immune response. We also discuss potential clinical applications for these autoantibodies, such as SCLC diagnosis, early detection, and therapy.

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

“…Immunologic processes causing autoantibody production are believed to be generated by the immune system in response to mutations, degradation, overexpression of proteins, and/or the release of proteins from damaged tissue (20)(21)(22)(23). Autoantibody production is also believed to be caused by mis-presentation or misfolding of proteins, which may be recognized by the immune system leading to autoantibody production and therefore, TAAs or proteins that have undergone alternate posttranslational modifications (PTM) may be recognized as nonautologous (17,19,24), that is, their phosphorylation, glycosylation, oxidation, or proteolytic cleavage could generate a neo-epitope or enhance self-epitope presentation and affinity to the MHC or T-cell receptor, inducing an immune response (25).…”

The Small Cell Lung Cancer-Specific Isoform of RE1-Silencing Transcription Factor (REST) Is Regulated By Neural-Specific Ser/Arg Repeat-Related Protein of 100 kDa (nSR100)

“…Database searches suggest that most of the PNS autoantigen genes contain the RE1 element (Supplementary Table S2). It was suggested that these antibodies have usage for early detection and diagnosis of SCLC (28). There is no information whether nSR100 affects the expression of PNS autoantigens, which contain the RE1 element.…”

Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report

“…Anti-Hu antibodies were detected in the patient's serum at a low titre, which is a highly uncommon finding, as the patient also had Hashimoto's thyroiditis. Low antibody titres are usually present in SCLC patients without autoimmune diseases (25). Those with SCLC and no clinical PNS have detectable anti-Hu antibodies in their serum in ~16-25% of the cases (25)(26)(27).…”

“…Low antibody titres are usually present in SCLC patients without autoimmune diseases (25). Those with SCLC and no clinical PNS have detectable anti-Hu antibodies in their serum in ~16-25% of the cases (25)(26)(27). When SCLC and PNS are found concurrently, the latter is usually mediated by a high titre of anti-Hu antibodies (28).…”