Current status and future prospects of cancer-derived immunoglobulins in pancreatic cancer

Abstract

Immunoglobulin (Ig) is an important part of the immune system, which is mainly produced by B cells to recognize and kill pathogens. In recent years, the concept of cancer-derived immunoglobulin (cIg) has been proposed. cIg is a special form of Ig found in tumor microenvironment, and the role of cIg in tumor development and potential clinical significance of cIg have attracted more attention recently. The discovery of cIg marks a new understanding of tumor immune response and provides new ideas for early diagnosis and individualized treatment of tumors. Pancreatic cancer is a highly malignant tumor that does not respond well to conventional treatment, and causes serious complications such as pancreatic cancer-associated diabetes. Therefore, exploring potential role of cIg in pancreatic cancer and the progression of pancreatic cancer-associated diabetes is expected to be a breakthrough to improve the diagnosis and treatment of pancreatic cancer and associated complications. This review aims to summarize current research status of cIg in the field of pancreatic cancer, and provide new ideas for modulating microenvironment of pancreatic cancer to improve diagnostic efficiency and therapeutic effect.

Keywords: cancer-derived immunoglobulin; microenvironment; pancreatic cancer.

Figure 1

Special glycosylation structure of cIg. CIg has a special sialylated N-glycan structure at Asn162 site, which can be specifically recognized by the monoclonal antibody RP215 to distinguish it from B-cell-derived Ig. The classical salivated N-glycan structure of Asn297 site in Ig Fc fragment is also demonstrated, which is responsible for maintaining Ig function.

Figure 2

cIg plays important role in pancreatic cancer through multiple mechanisms. CIg can directly promote the proliferation and invasion of pancreatic cancer cells. In addition, CIg can interact with NK cells and macrophages, participate in the reprogramming of PDAC immune microenvironment, and promote tumor immune escape. cIg promotes IgG expression in adjacent islet cells and affects normal hormone secretion, thus participating in the progression of pancreatic cancer-associated diabetes.