Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

Abstract

Traditionally, immunoglobulin (Ig) was believed to be produced by only B-lineage cells. However, increasing evidence has revealed a high level of Ig expression in cancer cells, and this Ig is named cancer-derived Ig. Further studies have shown that cancer-derived Ig shares identical basic structures with B cell-derived Ig but exhibits several distinct characteristics, including restricted variable region sequences and aberrant glycosylation. In contrast to B cell-derived Ig, which functions as an antibody in the humoral immune response, cancer-derived Ig exerts profound protumorigenic effects via multiple mechanisms, including promoting the malignant behaviors of cancer cells, mediating tumor immune escape, inducing inflammation, and activating the aggregation of platelets. Importantly, cancer-derived Ig shows promising potential for application as a diagnostic and therapeutic target in cancer patients. In this review, we summarize progress in the research area of cancer-derived Ig and discuss the perspectives of applying this novel target for the management of cancer patients.

Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia

“…This study is the first to demonstrate that all the five classes of Ig heavy chains and two types of Ig light chains could be expressed in non-B cells. IGHG has been reported in various non-B neoplastic cells and has been shown to promote malignant behaviors in cancer cells [ 8 ]. Similarly, we detected a high frequency of IGHG expression in myeloblasts.…”

“…Monoclonal immunoglobulin (Ig) gene rearrangement has been used as a diagnostic tool for B-cell lymphomas [ 7 ]. Although B-cells and plasma cells have been considered as the only source of Ig, a series of reports from our group and others have demonstrated that Ig could be expressed in many epithelial cancer cells [ 8 ], as well as in normal non-hematopoietic cells [ 9 , 10 , 11 ]. Moreover, other than acting as natural antibodies [ 12 , 13 ], non-B-derived Ig, especially IgG, with unique rearrangement patterns or glycosylation profile, has been shown to play a role in promoting cancer cell survival and proliferation, as well as cancer invasion and metastasis [ 8 , 14 ].…”

“…Although B-cells and plasma cells have been considered as the only source of Ig, a series of reports from our group and others have demonstrated that Ig could be expressed in many epithelial cancer cells [ 8 ], as well as in normal non-hematopoietic cells [ 9 , 10 , 11 ]. Moreover, other than acting as natural antibodies [ 12 , 13 ], non-B-derived Ig, especially IgG, with unique rearrangement patterns or glycosylation profile, has been shown to play a role in promoting cancer cell survival and proliferation, as well as cancer invasion and metastasis [ 8 , 14 ]. Non-B-derived Ig was frequently expressed in hematopoietic cells, including umbilical cord CD34 + stem/progenitor cells (IgM) [ 15 ], AML blasts (IgG, IgM, and Igκ) [ 16 , 17 , 18 ], and mature myeloid cells (IgM, and Igκ) [ 17 , 18 ].…”

Development of a Prognostic Nomogram for Acute Myeloid Leukemia on IGHD Gene Family

“…Importantly, cancer-derived immunoglobulins show potential applications as diagnostic and therapeutic targets for cancer patients. 31 Studies have shown that AML-derived IgG may be related to the occurrence of leukaemia and the progression of AML.…”

ImmunoTyper-SR: A Novel Computational Approach for Genotyping Immunoglobulin Heavy Chain Variable Genes using Short Read Data

“…While germline IGH genotypes have generally been overlooked in GWAS and other disease association studies, partially due to genotyping challenges, there is increasing interest in investigating the effect of IGH germline genetic variation on the adaptive immune system and disease[3, 5]. In fact IGHV germline genetic variation has recently been associated with clinical phenotypes including infectious disease and vaccine response [11, 12, 13, 14], autoimmune/inflammatory conditions[15, 16, 17], and cancer[18].…”