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Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development

Human immunoglobulin G (IgG) is the primary component of the human serum antibody fraction, representing about 75% of the immunoglobulins and 10–20% of the total circulating plasma proteins. Generally, IgG sequences are highly conserved, yet the four subclasses, IgG1, IgG2, IgG3, and IgG4, differ in...

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Autores principales: Kdimati, Said, Mullins, Christina Susanne, Linnebacher, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583861/
https://www.ncbi.nlm.nih.gov/pubmed/34769026
http://dx.doi.org/10.3390/ijms222111597
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author Kdimati, Said
Mullins, Christina Susanne
Linnebacher, Michael
author_facet Kdimati, Said
Mullins, Christina Susanne
Linnebacher, Michael
author_sort Kdimati, Said
collection PubMed
description Human immunoglobulin G (IgG) is the primary component of the human serum antibody fraction, representing about 75% of the immunoglobulins and 10–20% of the total circulating plasma proteins. Generally, IgG sequences are highly conserved, yet the four subclasses, IgG1, IgG2, IgG3, and IgG4, differ in their physiological effector functions by binding to different IgG-Fc receptors (FcγR). Thus, despite a similarity of about 90% on the amino acid level, each subclass possesses a unique manner of antigen binding and immune complex formation. Triggering FcγR-expressing cells results in a wide range of responses, including phagocytosis, antibody-dependent cell-mediated cytotoxicity, and complement activation. Textbook knowledge implies that only B lymphocytes are capable of producing antibodies, which recognize specific antigenic structures derived from pathogens and infected endogenous or tumorigenic cells. Here, we review recent discoveries, including our own observations, about misplaced IgG expression in tumor cells. Various studies described the presence of IgG in tumor cells using immunohistology and established correlations between high antibody levels and promotion of cancer cell proliferation, invasion, and poor clinical prognosis for the respective tumor patients. Furthermore, blocking tumor-cell-derived IgG inhibited tumor cells. Tumor-cell-derived IgG might impede antigen-dependent cellular cytotoxicity by binding antigens while, at the same time, lacking the capacity for complement activation. These findings recommend tumor-cell-derived IgG as a potential therapeutic target. The observed uniqueness of Ig heavy chains expressed by tumor cells, using PCR with V(D)J rearrangement specific primers, suggests that this specific part of IgG may additionally play a role as a potential tumor marker and, thus, also qualify for the neoantigen category.
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spelling pubmed-85838612021-11-12 Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development Kdimati, Said Mullins, Christina Susanne Linnebacher, Michael Int J Mol Sci Review Human immunoglobulin G (IgG) is the primary component of the human serum antibody fraction, representing about 75% of the immunoglobulins and 10–20% of the total circulating plasma proteins. Generally, IgG sequences are highly conserved, yet the four subclasses, IgG1, IgG2, IgG3, and IgG4, differ in their physiological effector functions by binding to different IgG-Fc receptors (FcγR). Thus, despite a similarity of about 90% on the amino acid level, each subclass possesses a unique manner of antigen binding and immune complex formation. Triggering FcγR-expressing cells results in a wide range of responses, including phagocytosis, antibody-dependent cell-mediated cytotoxicity, and complement activation. Textbook knowledge implies that only B lymphocytes are capable of producing antibodies, which recognize specific antigenic structures derived from pathogens and infected endogenous or tumorigenic cells. Here, we review recent discoveries, including our own observations, about misplaced IgG expression in tumor cells. Various studies described the presence of IgG in tumor cells using immunohistology and established correlations between high antibody levels and promotion of cancer cell proliferation, invasion, and poor clinical prognosis for the respective tumor patients. Furthermore, blocking tumor-cell-derived IgG inhibited tumor cells. Tumor-cell-derived IgG might impede antigen-dependent cellular cytotoxicity by binding antigens while, at the same time, lacking the capacity for complement activation. These findings recommend tumor-cell-derived IgG as a potential therapeutic target. The observed uniqueness of Ig heavy chains expressed by tumor cells, using PCR with V(D)J rearrangement specific primers, suggests that this specific part of IgG may additionally play a role as a potential tumor marker and, thus, also qualify for the neoantigen category. MDPI 2021-10-27 /pmc/articles/PMC8583861/ /pubmed/34769026 http://dx.doi.org/10.3390/ijms222111597 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kdimati, Said
Mullins, Christina Susanne
Linnebacher, Michael
Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development
title Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development
title_full Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development
title_fullStr Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development
title_full_unstemmed Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development
title_short Cancer-Cell-Derived IgG and Its Potential Role in Tumor Development
title_sort cancer-cell-derived igg and its potential role in tumor development
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583861/
https://www.ncbi.nlm.nih.gov/pubmed/34769026
http://dx.doi.org/10.3390/ijms222111597
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