Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review)

Abstract

For early detection of cancer, education and screening are important, but the most critical factor is the development of early diagnostic tools. Methods that recognize the warning signs of cancer and take prompt action lead to an early diagnosis; simple tests can identify individuals in a healthy population who have the disease but have not developed symptoms. Early detection of cancer is significant and is one of the most promising approaches by which to reduce the growing cancer burden and guide curative treatment. The early diagnosis of patients with breast cancer is challenging, since it is the most common cancer in women worldwide. Despite the advent of mammography in screening for breast cancer, low-resource, low-cost alternative tools must be implemented to complement mammography findings. IgM is part of the first line of defense of an organism and is responsible for recognizing and eliminating infectious particles and removing transformed cells. Most studies on breast cancer have focused on the development of IgG-like molecules as biomarkers or as a treatment for the advanced stages of cancer, but autoantibodies (IgM) and tumor-associated antigens (proteins or carbohydrates with aberrant structures) have not been examined as early diagnostic tools for breast cancer. The present review summarizes the function of natural and adaptive IgM in eliminating cancer cells in the early stages of pathology and their value as early diagnostic tools. IgM, as a component of the immune system, is being used to identify tumor-associated antigens and tumor-associated carbohydrate antigens.

PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5–Dependent Mechanism

“…Natural antibody production is critical for protection against infectious diseases, allergy, cancer, and atherosclerosis (8, 10, 11, 69, 70). B-1 cells play a crucial role in producing natural Abs, including phosphorylcholine (PC)–specific Ab (4).…”

“…The B-1 cell subset produces the majority of natural Abs in the serum, of which IgM is the principal isotype (4, 5, 23–26). Natural Abs are directed against multiple specificities, including oxidized LDL (OxLDL), phosphatidylcholine (PtC), phosphorylcholine (PC), malondialdehyde (MDA), oxidized cardiolipin (OxCL), 4-hydroxynonenal (4-HNE), and Thy-1 (CD90), as well as tumor associated antigens (10, 11, 13, 27). …”

Complement in cancer: untangling an intricate relationship

“…Whereas complement activation in response to natural IgM antibodies against tumour antigens as well as direct cleavage of C3 and C5 by tumour-derived proteases have been detected in cancer settings 121 , novel insights into the mechanisms driving complement activation by specific cancer types are essential for rationalizing therapeutic approaches aimed at manipulating the complement system in cancer. A variety of complement inhibitors that target distinct stages and pathways of the complement cascade are under development.…”

In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway

“…However, extraction of EAAs from the sera of patients with cancer to activate the humoral immune response against some malignant tumors has been considered. A few EAAs selected from patients, such as SC-1 (anti-CD55), PAM-1 [anti-cysteine-rich fibroblast growth factor (anti-CFR1)], and PAT-SM6 (anti-GRP78), act directly against tumors and effectively kill them via antibody-mediated cellular cytotoxicity (8). In addition, a natural human IgM autoantibody (PAT-SM6) selected from patients' sera against the cell surface GRP78 protein provides therapeutic effects for patients with cancer (9,10).…”