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      Antibodies as biomarkers for cancer risk: a systematic review

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          Abstract

          Increasing evidence has linked the humoral immune response with the development of various cancers. Therefore, there is growing interest in investigating the predictive value of antibodies to assess overall and tissue site-specific cancer risk. Given the large amount of antibody types and the broad scope of the search (i.e. cancer risk), the primary aim of this systematic review was to present an overview of the most researched antibodies (i.e. immunoglobulin (Ig) isotypes (IgG, IgM, IgA, and IgE), tumour and self-antigen-reactive antibodies, infection-related antibodies) in relation to overall and site-specific cancer risk. We identified various antibody types that have been associated with the risk of cancer. While no significant associations were found for IgM serum levels, studies found an inconsistent association among IgE, IgA, and IgG serum levels in relation to cancer risk. When evaluating antibodies against infectious agents, most studies reported a positive link with specific cancers known to be associated with the specific agent recognized by serum antibodies (i.e. helicobacter pylori and gastric cancer, hepatitis B virus and hepatocellular carcinoma, and human papillomavirus and cervical cancer). Several reports identified autoantibodies, as single biomarkers (e.g. anti-p53, anti-MUC1, and anti-CA125) but especially in panels of multiple autoantibodies, to have potential as diagnostic biomarkers for specific cancer types. Overall, there is emerging evidence associating certain antibodies to cancer risk, especially immunoglobulin isotypes, tumour-associated antigen-specific, and self-reactive antibodies. Further experimental studies are necessary to assess the efficacy of specific antibodies as markers for the early diagnosis of cancer.

          Abstract

          The humoral immune response has been consistently linked with the development of various cancers. Therefore, increasing evidence has investigated the predictive value of antibodies to assess site-specific cancer risk. In the current study, we review the current evidence for the association between the most researched antibodies and risk of site-specific cancers

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          The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

          Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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            Structure and function of immunoglobulins.

            Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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              B cells, plasma cells and antibody repertoires in the tumour microenvironment

              Recent data show that B cells and plasma cells located in tumours or in tumour-draining lymph nodes can have important roles in shaping antitumour immune responses. In tumour-associated tertiary lymphoid structures, T cells and B cells interact and undergo cooperative selection, specialization and clonal expansion. Importantly, B cells can present cognate tumour-derived antigens to T cells, with the functional consequences of such interactions being shaped by the B cell phenotype. Furthermore, the isotype and specificity of the antibodies produced by plasma cells can drive distinct immune responses. Here we summarize our current knowledge of the roles of B cells and antibodies in the tumour microenvironment. Moreover, we discuss the potential of using immunoglobulin repertoires as a source of tumour-specific receptors for immunotherapy or as biomarkers to predict the efficacy of immunotherapeutic interventions.
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                Author and article information

                Contributors
                Journal
                Clin Exp Immunol
                Clin Exp Immunol
                cei
                Clinical and Experimental Immunology
                Oxford University Press (US )
                0009-9104
                1365-2249
                July 2022
                04 April 2022
                04 April 2022
                : 209
                : 1
                : 46-63
                Affiliations
                Translational Oncology and Urology Research (TOUR), Centre for Cancer, Society, and Public Health, School of Cancer and Pharmaceutical Sciences, King’s College London , London, UK
                St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London , London SE1 9RT, UK
                Higher Degree by Research, University of South Australia , Adelaide, Australia
                Cancer Epidemiology and Population Health Research Group, University of South Australia , Adelaide, SE, Australia
                Higher Degree by Research, University of South Australia , Adelaide, Australia
                St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London , London SE1 9RT, UK
                Translational Oncology and Urology Research (TOUR), Centre for Cancer, Society, and Public Health, School of Cancer and Pharmaceutical Sciences, King’s College London , London, UK
                Translational Oncology and Urology Research (TOUR), Centre for Cancer, Society, and Public Health, School of Cancer and Pharmaceutical Sciences, King’s College London , London, UK
                Author notes
                Correspondence: Aida Santaolalla, Translational Oncology and Urology Research (TOUR), Centre for Cancer, Society, and Public Health, School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK. Email: Aida.santaolalla@ 123456kcl.ac.uk

                Maria J Monroy-Iglesias and Silvia Crescioli contributed equally to this work as first co-authors

                Author information
                https://orcid.org/0000-0002-4100-7810
                https://orcid.org/0000-0003-2417-3275
                Article
                uxac030
                10.1093/cei/uxac030
                9307228
                35380164
                63263f5c-fa11-4972-9f2a-b130a2e37762
                © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 December 2021
                : 11 March 2022
                : 30 March 2022
                : 13 May 2022
                Page count
                Pages: 18
                Funding
                Funded by: National Institute for Health Research, DOI 10.13039/501100000272;
                Funded by: NHS Foundation Trust;
                Funded by: King's College London, DOI 10.13039/501100000764;
                Award ID: IS-BRC-1215-20006
                Funded by: NIHR Department of Health;
                Categories
                Review Series: Immune cell-antibody interactions in health and disease (Series Editors: Sophia Karagiannis and James Arnold)
                Reviews
                AcademicSubjects/MED00010
                AcademicSubjects/MED00160
                AcademicSubjects/MED00690
                AcademicSubjects/MED00730

                Immunology
                antibodies,biomarkers,cancer,early detection,tumor -associated antigens,immunoglobulin
                Immunology
                antibodies, biomarkers, cancer, early detection, tumor -associated antigens, immunoglobulin

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