Prognostic and Diagnostic Value of Spontaneous Tumor‐Related Antibodies

Abstract

There is an urgent need for earlier diagnosis of malignancies and more stringent monitoring of relapses after antitumor therapy. In addition, new prognostic markers are needed for risk stratification and design of individualized cancer therapies. New diagnostic and prognostic parameters should overcome the impairments of current standards in a cost-effective manner. Serological approaches measuring spontaneous antibody responses against tumor-associated antigens could be of use as diagnostic and prognostic markers and could also be employed to evaluate response to therapy in cancer patients. Autoantibodies have been suggested to be of frequent and specific occurrence in patients with malignancies and to correlate with clinical parameters. Screening the relevant literature on this topic, we suggest that the analysis of single antibody specificities is unlikely to provide sufficient diagnostic and prognostic accuracy. The combined analysis of autoantibodies targeting different antigens, however, may reach high sensitivity and specificity. In addition, screening cancer patients for autoantibodies might identify subgroups with high relapse risk and a worse prognosis. Larger prospective trials should be initiated to identify sets of tumor-associated autoantibodies suited for the use in diagnostic algorithms for cancer detection and followup.

Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation

“…AlloSCT has been suggested to improve overall survival and to achieve cures in patients through immune mechanisms involving a graft-versus-myeloma (GvM) effect [22]; however, the targets of these immune reactions and their quality remain poorly understood. It has been shown for multiple tumor types that patients are capable of developing spontaneous antibody responses against intracellular tumor proteins [1,23]. The present study constitutes the first longitudinal analysis of antibody responses against the predominantly intracellular cancertestis antigen family in a human malignancy.…”

“…A subgroup of cancer patients, at one point during the course of their disease, will develop spontaneous antibody responses against antigens expressed by their own tumors [1]. Unfortunately, little is known about the quality of these responses over time, their immunological properties, and especially their fine specificity.…”

SOX2 Autoantibodies As Noninvasive Serum Biomarker for Breast Carcinoma

“…Lu and colleagues (16) reported that the detection of p53-Abs had an ROC-AUC of 0.48 (P ¼ 0.538) whereas the combination of p53-Abs and HER2-Abs had an ROC-AUC of 0.61 (P ¼ 0.006), in discriminating advanced-stage breast cancer patients from nonmalignant disease and healthy controls. To meet the stringent sensitivity and accuracy requirements for a diagnostic assay, we would recommend that SOX2-Abs are assayed in combination with a panel of other serum biomarkers, such as antibodies to p53, c-myc, and survivin (17)(18)(19).…”

Detection of tumor-associated antigens in culture supernatants using autoantibodiesin sera from patients with bladder cancer

“…Hundreds of tumor-associated antibodies have been identified, and the potential for using AAbs as a novel biomarker useful for cancer diagnosis has been discussed (17). Furthermore, recent studies based on AAb profiling of cancer patients have suggested that AAbs may not be only diagnostic but also prognostic biomarkers (24). In this study, we performed two-dimensional gel electrophoresis (2-DE) combined with immunoblot analysis to identify tumor-associated secreted antigenic proteins that elicit a humoral response in sera from BC patients.…”

“…It has been reported that the overexpression of calreticulin was detected in tumor tissues and their sera of hepatocellular, colon, and lung cancers (18,45,49), and associated with the migration and proliferation of tumor cells and a poorer prognosis in esophageal, gastric, and breast AAbs against tumor-associated antigens have been identified in sera from patients with colon, breast, lung, ovary, and bladder cancers (4,7,16,36,50). Thus, the application of the humoral immune response for the detection of cancer biomarkers has a great potential and has been suggested as ideal screening for cancer diagnosis and their prognostic value (17,24). Furthermore, the immune system is especially well adapted for the early detection of cancer, because AAbs can be detected before the appearance of other biomarkers or phenotypic alternations in an early stage of tumorigenesis (19).…”