Antibody Diversity in Cancer: Translational Implications and Beyond

Abstract

Patients with cancer tend to develop antibodies to autologous proteins. This phenomenon has been observed across multiple cancer types, including bladder, lung, colon, prostate, and melanoma. These antibodies potentially arise due to induced inflammation or an increase in self-antigens. Studies focusing on antibody diversity are particularly attractive for their diagnostic value considering antibodies are present at an early diseased stage, serum samples are relatively easy to obtain, and the prevalence of antibodies is high even when the target antigen is minimally expressed. Conversely, the surveillance of serum proteins in cancer patients is relatively challenging because they often show variability in expression and are less abundant. Moreover, an antibody's presence is also useful as it suggests the relative immunogenicity of a given antigen. For these reasons, profiling antibodies' responses is actively considered to detect the spread of antigens following immunotherapy. The current review focuses on expanding the knowledge of antibodies and their diversity, and the impact of antibody diversity on cancer regression and progression.

Keywords: B cell; T cell; antibody; cancer; immunotherapy; macrophage; monoclonal antibodies; vaccines.

Figure 1

Antibodies have a constant domain, variable domain, heavy chains, and light chains.

Figure 2

Provenge, the first FDA-approved cancer vaccine, works through utilizing a recipient’s immune cells and prostatic acid phosphatase (PAP) as part of the vaccine to stimulate T cells to attack prostate cancer cells. Created with BioRender.com for this review.

Figure 3

Immune checkpoint therapy. Created with BioRender.com for this review. (A) Cytotoxic (CD8+) T cells possess a vital anti-proliferative function. However, cancer cells utilize Program Death-1 Ligand (PD-L1) to deceive the immune system into thinking they are healthy cells, causing the CD8+ cells to become anergic. Pembrolizumab and Nivolumab work by blocking PD-1 interaction with PD-L1. (B) When CD28 (co-stimulatory signal) on a helper (CD4+) T cell or CD8+ T cell binds to CD80/86 on an antigen-presenting cell (APC), it activates naïve T cells. However, CTLA-4 competes against CD28 for CD80/86 binding. The binding of CTLA-4 to CD80/86 inhibits the activation of naïve T cells. Ipilimumab inhibits CTLA-4, relieving immunosuppression.