Survey of autoantibody responses against tumor-associated antigens in thyroid cancer

Ābols, Artūrs; Ducena, Kristine; Zayakin, Pawel; Siliņa, Karīna; Kalniņa, Zane; Sadovska, Lilite; Tars, Juris; Vilmanis, Jānis; Narbuts, Zenons; Eglītis, Jānis; Pīrāgs, Valdis; Linē, Aija

doi:10.3233/cbm-140413

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…Among them were several previously known cancer antigens as well as novel peptides. CTAG1B, BRCA2, and SPAG8 have been previously shown to induce humoral immune response in BC ( 27 – 29 ) and other cancer patients ( 25 , 27 , 30 ), ANKRD30BL and COPS4 were previously found to elicit autoantibody response in gastric and thyroid cancer and melanoma ( 24 , 26 ). Artificial peptides AP1292, AP1775 and AP1361 were reacting with sera from gastric cancer patients in our previous studies ( 24 ) and may represent neoantigens or mimotopes of other cancer-associated antigens.…”

Section: Resultsmentioning

confidence: 99%

Antigen Specificity and Clinical Significance of IgG and IgA Autoantibodies Produced in situ by Tumor-Infiltrating B Cells in Breast Cancer

et al. 2018

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An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ. The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyzed to investigate relationships between autoantibodies and the clinical, histological and immunological features of tumors. Our data show that >84% of the BC samples tested contain autoantibodies to one or more antigens on the array, with ANKRD30BL, COPS4, and CTAG1B being most frequently reactive. Ex vivo TIL-B responses were uncoupled from systemic humoral responses in the majority of cases. A comparison of autoantibody frequencies in supernatants and plasma from patients and controls identified eight antigens that elicit BC-associated autoantibody responses. The overall prevalence of IgG and IgA autoantibodies was similar and while IgG and IgA responses were not linked they did correlate with distinct clinical, pathological and immunological features. Higher levels of ex vivo IgG responses to BC-associated antigens were associated with shorter recurrence-free survival (RFS), HER2 overexpression and lower tumor-infiltrating CD8+ T cell counts. Higher IgA levels were associated with estrogen and progesterone receptor-negative cancers but were not significantly associated with RFS. Furthermore, ex vivo IgA but not IgG autoantibodies reactive to BC-associated antigens were linked with germinal center and early memory B cell maturation and the presence of tertiary lymphoid structures suggesting that these TIL-B are activated in the tumor microenvironment. Overall, our results extend the current understanding of the antigen specificity, the biological and the clinical significance of IgG and IgA autoantibodies produced by BC TIL-B in situ.

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Section: Resultsmentioning

confidence: 99%

Antigen Specificity and Clinical Significance of IgG and IgA Autoantibodies Produced in situ by Tumor-Infiltrating B Cells in Breast Cancer

et al. 2018

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“…However, autoantigenic repertoires of many human neoplasms, eg, endocrine tumors, have not been studied in sufficient detail. Only two top-down studies identified several antigens eliciting autoantibody responses in anaplastic (25) and papillary (26) thyroid carcinomas, and few additional antigens were implicated in thyroid carcinomas in bottom-up setting (15,(27)(28)(29)(30). Importantly, none of these studies focused on encapsulated follicular-patterned lesions.…”

Section: Discussionmentioning

confidence: 90%

Serum Immunoproteomics Combined With Pathological Reassessment of Surgical Specimens Identifies TCP-1ζ Autoantibody as a Potential Biomarker in Thyroid Neoplasia

Belousov

Bogolyubova

et al. 2015

The Journal of Clinical Endocrinology &Amp; Metabolism

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We identified TCP-1ζ autoantibodies as a potential biomarker for presurgical discrimination between benign and malignant encapsulated follicular-patterned thyroid tumors. Our results suggest the use of nonconservative morphological criteria for diagnosis of malignant EnFPT in biomarker identification studies and provide a peculiar example of uncovering the diagnostic potential of a candidate biomarker using incorporation of pathological reassessment in the pipeline of immunoproteomic research.

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“…Apart from TAAs identified in a few top-down studies carried out at a whole-transcriptome/proteome-level, several additional TAAs were also implicated in thyroid neoplasia either in bottom-up or in a «semi bottom-up» (i.e., selection of TAA candidates from a set of pre-selected protein features) settings. In such a way, Abols et al [ 140 ] used a low-density phage-displayed TAA microarray comprising 65 candidate TAA features in order to test their serological reactivity in 53 patients with various thyroid carcinomas, 90 FTA patients, and 96 cancer-free individuals. Although the differences in frequencies of the cognate TAA-AAbs’ reactivity between studied groups reached statistical significance for only a single TAA (i.e., cancer-testis antigen GAGE1, Figure 2 ), the optimal cut-off values of combined serum score calculated for a six-antigen TAA panel preferentially reacted with thyroid cancer sera (i.e., GAGE1, COP9 signalosome complex subunit 4 (COPS4) and four artificial peptides most likely encoding the mimotopes of unknown antigens) discriminated the combined thyroid cancer group from FTA and healthy individuals with DSp of 97% and 90%, respectively, and DSn of 25% in both comparisons.…”

Section: The Tumor-associated Antigens (Taas) and Their Cognate Autoa...mentioning

confidence: 99%

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

Belousov

2022

Biomedicines

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The Autoantibodies targeting Tumor-Associated Antigens (TAA-AAbs) emerge as a result of a variety of tumor-related immunogenic stimuli and may be regarded as the eyewitnesses to the anti-tumor immune response. TAA-AAbs may be readily detected in peripheral blood to unveil the presence of a particular TAA-expressing tumor, and a fair number of TAAs eliciting the tumor-associated autoantibody response have been identified. The potential of TAA-AAbs as tumor biomarkers has been extensively studied in many human malignancies with a major influence on public health; however, tumors of the endocrine system, and, in particular, the well-differentiated follicular cell-derived thyroid neoplasms, remain understudied in this context. This review provides a detailed perspective on and legitimate rationales for the potential use of TAA-AAbs in thyroid neoplasia, with particular reference to the already established diagnostic implications of the TAA-AAbs in human cancer, to the windows for improvement and diagnostic niches in the current workup strategies in nodular thyroid disease and differentiated thyroid cancer that TAA-AAbs may successfully occupy, as well as to the proof-of-concept studies demonstrating the usefulness of TAA-AAbs in thyroid oncology, particularly for the pre-surgical discrimination between tumors of different malignant potential in the context of the indeterminate results of the fine-needle aspiration cytology.

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Survey of autoantibody responses against tumor-associated antigens in thyroid cancer

Abstract: Although six TAAs, including one CTA, showed thyroid cancer-associated reactivity, overall, spontaneous humoral immune responses against TAAs are rare in thyroid cancer and their utility for the development of non-invasive assay for the differential diagnosis of thyroid nodules is limited.

Cited by 9 publications

References 30 publications

Antigen Specificity and Clinical Significance of IgG and IgA Autoantibodies Produced in situ by Tumor-Infiltrating B Cells in Breast Cancer

Antigen Specificity and Clinical Significance of IgG and IgA Autoantibodies Produced in situ by Tumor-Infiltrating B Cells in Breast Cancer

Serum Immunoproteomics Combined With Pathological Reassessment of Surgical Specimens Identifies TCP-1ζ Autoantibody as a Potential Biomarker in Thyroid Neoplasia

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

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