Autoantibody Production in Cancer - The Humoral Immune Response toward Autologous Antigens in Cancer Patients

Published on May 1, 2016in Autoimmunity Reviews7.716
· DOI :10.1016/j.autrev.2016.01.017
Pauline Zaenker3
Estimated H-index: 3
(ECU: Edith Cowan University),
Elin S. Gray31
Estimated H-index: 31
(ECU: Edith Cowan University),
Melanie Ziman24
Estimated H-index: 24
A link between autoimmune responses and cancer via autoantibodies was first described in the 1950s. Since, autoantibodies have been studied for their potential use as cancer biomarkers, however the exact causes of their production remain to be elucidated. This review summarizes current theories of the causes of autoantibody production in cancer, namely: 1) defects in tolerance and inflammation, 2) changes in protein expression levels, 3) altered protein structure, and 4) cellular death mechanisms. We also highlight the need for further research into this field to improve our understanding of autoantibodies as biomarkers for cancer development and progression.
  • References (78)
  • Citations (46)
📖 Papers frequently viewed together
80 Citations
229 Citations
209 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Karen S. AndersonH-Index: 59
#2Daniel W. Cramer (Harvard University)H-Index: 75
Last. Joshua LaBaerH-Index: 43
view all 9 authors...
Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5177 candidate tumor antigens with sera from patients with serous ovarian cancer (n = 34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n = 60 cases/60 controls). Twelve pot...
40 CitationsSource
#1Diana A. Alvarez Arias (Harvard University)H-Index: 2
#2Hye-Jung Kim (Harvard University)H-Index: 20
Last. Harvey Cantor (Harvard University)H-Index: 76
view all 7 authors...
Tumor growth is associated with the inhibition of host antitumor immune responses that can impose serious obstacles to cancer immunotherapy. To define the potential contribution of Qa-1–restricted CD8 regulatory T cells (Treg) to the development of tumor immunity, we studied B6.Qa-1 D227K mice that harbor a point mutation in the MHC class Ib molecule Qa-1 that impairs CD8 Treg suppressive activity. Here, we report that the growth of B16 melanoma is substantially delayed in these Qa-1–mutant mice...
19 CitationsSource
#1Christine G. Joseph (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 2
#2Erika Darrah (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 14
Last. Antony Rosen (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 62
view all 15 authors...
Autoimmune diseases are thought to be initiated by exposures to foreign antigens that cross-react with endogenous molecules. Scleroderma is an autoimmune connective tissue disease in which patients make antibodies to a limited group of autoantigens, including RPC1, encoded by the POLR3A gene. As patients with scleroderma and antibodies against RPC1 are at increased risk for cancer, we hypothesized that the “foreign” antigens in this autoimmune disease are encoded by somatically mutated genes in ...
204 CitationsSource
#1Cyriac Kandoth (WashU: Washington University in St. Louis)H-Index: 42
#2Michael D. McLellan (WashU: Washington University in St. Louis)H-Index: 59
Last. Li Ding (WashU: Washington University in St. Louis)H-Index: 88
view all 19 authors...
As part of The Cancer Genome Atlas Pan-Cancer effort, data analysis for point mutations and small indels from 3,281 tumours and 12 tumour types is presented; among the findings are 127 significantly mutated genes from cellular processes with both established and emerging links in cancer, and an indication that the number of driver mutations required for oncogenesis is relatively small.
1,870 CitationsSource
#1Ludmil B. Alexandrov (Wellcome Trust Sanger Institute)H-Index: 45
#2Serena Nik-Zainal (Wellcome Trust)H-Index: 39
Last. Michael R. Stratton (University of Barcelona)H-Index: 139
view all 71 authors...
All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, wher...
3,544 CitationsSource
#1Brian Burford ('KCL': King's College London)H-Index: 6
#2A Gentry-Maharaj (UCL: University College London)H-Index: 13
Last. Joy Burchell ('KCL': King's College London)H-Index: 53
view all 30 authors...
Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer
36 CitationsSource
#1Emily Stamell Ruiz (Albert Einstein College of Medicine)H-Index: 5
#2Jedd D. WolchokH-Index: 105
Last. Isaac Brownell (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 6
view all 5 authors...
The clearance of nonirradiated tumors after localized radiation therapy is known as the abscopal effect. Activation of an antitumor immune response has been proposed as a mechanism for the abscopal effect. Here we report a patient with metastatic melanoma who received palliative radiation to his primary tumor with subsequent clearance of all his nonirradiated in-transit metastases. Anti-MAGEA3 antibodies were found upon serological testing, demonstrating an association between the abscopal effec...
229 CitationsSource
#1Pawel Zayakin (Latvian Biomedical Research and Study centre)H-Index: 6
#2Guntis Ancāns (LU: University of Latvia)H-Index: 1
Last. Aija Linē (Latvian Biomedical Research and Study centre)H-Index: 16
view all 15 authors...
Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage–antigen microarrays and exploit...
40 CitationsSource
B cells infiltrating into solid tumors are poorly investigated despite their described positive prognostic value. Whether this antitumor potential comes from either the antigen presentation or the antibody production capacity of B cells, or both, is unknown. Our recently published method on tumor-infiltrating B lymphocyte cloning may prove helpful in unraveling the actual relevance of these cells for tumor development and response to therapy.
30 CitationsSource
OBJECTIVE • To assess whether men undergoing prostate biopsies for raised prostate-specific antigen (PSA) concentrations were adequately counselled before their first PSA test. PATIENTS AND METHODS • Men were given a PSA information sheet and interviewed immediately before undergoing transrectal ultrasonography (TRUS)/prostate biopsy. • Information collected included whether they had been informed of the test, whether they were aware of TRUS/biopsy and whether possible treatments for prostate ca...
7 CitationsSource
Cited By46
#1Danilo Echeverri (UdeA: University of Antioquia)
#2Monika Garg (MPG: Max Planck Society)H-Index: 1
Last. Jahir Orozco (UdeA: University of Antioquia)H-Index: 2
view all 4 authors...
Abstract Glycosylphosphatidylinositol anchored proteins (GPI-APs) are natural conjugates in the plasma membrane of eukaryotic cells that result from the attachment of a glycolipid to the C-terminus of many proteins. GPI-APs play a crucial role in cell signaling and adhesion and have implications in health and diseases. GPI-APs and GPIs without protein (free GPIs) are found in abundance on the surface of the protozoan parasite Toxoplasma gondii. The detection of anti-GPI IgG and IgM antibodies al...
#1William S. Chen (UCSF: University of California, San Francisco)H-Index: 4
#2Winston HaynesH-Index: 13
Last. Ivan Garcilazo Perez (UCLA: University of California, Los Angeles)
view all 30 authors...
Although the importance of T-cell immune responses is well appreciated in cancer, autoantibody responses are less well-characterized. Nevertheless, autoantibody responses are of great interest, as they may be concordant with T-cell responses to cancer antigens or predictive of response to cancer immunotherapies. We performed serum epitope repertoire analysis (SERA) on a total of 1,229 serum samples obtained from a cohort of 72 men with metastatic castration-resistant prostate cancer (mCRPC) and ...
#1Sahar Ghassem-Zadeh (UNIL: University of Lausanne)H-Index: 1
#2Katrin Hufnagel (DKFZ: German Cancer Research Center)H-Index: 2
Last. Christoph Eckert (University Hospital Heidelberg)H-Index: 1
view all 13 authors...
Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients’ sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays we...
#1Pey Yee Lee (UKM: National University of Malaysia)H-Index: 2
#2Neda Saraygord-Afshari (IUMS: Iran University of Medical Sciences)H-Index: 2
Last. Teck Yew Low (UKM: National University of Malaysia)H-Index: 19
view all 3 authors...
Abstract Two-dimensional gel electrophoresis (2-DE) is a technique that has been widely applied in a variety of proteomics studies. It is capable of resolving complex protein mixtures into individual protein spots based on their isoelectric point and molecular weight, enabling large-scale analysis of protein expression patterns for deciphering their changes in different biological conditions. 2-DE is a powerful tool that empowers researchers to perform differential qualitative and quantitative p...
#1Winston HaynesH-Index: 13
#2Kathy KamathH-Index: 1
Last. John C ShonH-Index: 1
view all 4 authors...
Identification of the antigens associated with antibodies is vital to understanding immune responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a proteome scale could enable broader identification of antigens that are responsible for generating an immune response or driving a disease state. Although targeted tests for known antigens can be straightforward, discovering antigens at a proteome scale using protein and peptide arrays is time consuming and expensive...
1 CitationsSource
#1Young Nam Kwon (Kyung Hee University)H-Index: 2
#2Jiwon Koh (Seoul National University Hospital)H-Index: 6
Last. Sung-Min Kim (SNU: Seoul National University)H-Index: 16
view all 6 authors...
Abstract Background : Myelin oligodendrocyte glycoprotein immunoglobulin-G (IgG)-associated encephalomyelitis (MOG-EM) is a distinct inflammatory demyelinating disease. We present an unusual MOG-EM cases with concomitant T-cell lymphoma. Case report : A 38-year-old Caucasian male presented with bilateral optic neuritis and multifocal transverse myelitis. He tested positive for MOG-IgG1 and his neurologic symptoms improved with high dose steroid treatment. Six months after his first MOG-EM sympto...
#1Vanessa M. Beutgen (University of Mainz)H-Index: 1
#2Carsten Schmelter (University of Mainz)H-Index: 3
Last. Franz H. Grus (University of Mainz)H-Index: 34
view all 4 authors...
Objectives Primary open‐angle glaucoma (POAG) is a neurodegenerative disorder leading to a gradual vision loss caused by progressive damage to the optic nerve. Immunological processes are proposed to be involved in POAG pathogenesis. Altered serological autoantibody levels have been frequently reported, but complete analyses of the natural autoantibodies with respect to disease‐related alterations are scarce. Here, we provide an explorative analysis of pathways and biological processes that may ...
#1Yang Li (SJTU: Shanghai Jiao Tong University)H-Index: 16
#2Cheng-qiang Li (SJTU: Shanghai Jiao Tong University)
Last. Shengce Tao (SJTU: Shanghai Jiao Tong University)H-Index: 22
view all 7 authors...
Abstract Background Autoantibodies against tumor associated antigens are highly related to cancer progression. Autoantibodies could serve as indicators of tumor burden, and have the potential to monitor the response of treatment and tumor recurrence. However, how the autoantibody repertoire changes in response to cancer treatment are largely unknown. Methods Sera of five lung adenocarcinoma patients before and after surgery, were collected longitudinally. These sera were analyzed on a human prot...
#1Elena PoliH-Index: 2
#2Angelica ZinH-Index: 9
Last. Gianni BisognoH-Index: 33
view all 8 authors...
Insulin-like growth factor-binding protein 2 (IGFBP2) is a tumor-associated protein measurable in patients’ biopsies and blood samples. Increased IGFBP2 expression correlates with tumor severity in rhabdomyosarcoma (RMS). Thus, we examined the plasmatic IGFBP2 levels in 114 RMS patients and 15 healthy controls by ELISA assay in order to evaluate its value as a plasma biomarker for RMS. Additionally, we looked for the presence of a humoral response against IGBFP2 protein measurable by the product...