Journal Article

Cancer-associated mucins: role in immune modulation and metastasis

Cannon, Andrew, Gautam, Shailendra K, Banerjee, Kasturi, Hall, Bradley R, Aithal, Abhijit, Kumar, Sushil, Jain, Maneesh, Batra, Surinder K, Bhatia, Rakesh, Thompson, Christopher, Solheim, Joyce C

2019

Overview

Mucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC1-mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecules. MUC1 and MUC16 bind siglecs and mask Toll-like receptors (TLRs), respectively, on DCs promoting an immature DC phenotype that in turn reduces T cell effector functions. Mucins, such as MUC1, MUC2, MUC4, and MUC16, interact with or form aggregates with neutrophils, macrophages, and platelets, conferring protection to cancer cells during hematological dissemination and facilitate their spread and colonization to the metastatic sites. On the contrary, poor glycosylation of MUC1 and MUC4 at the tandem repeat region (TR) generates cancer-specific immunodominant epitopes. The presence of MUC16 neo-antigen-specific T cell clones and anti-MUC1 antibodies in cancer patients suggests that mucins can serve as potential targets for developing cancer therapeutics. The present review summarizes the molecular events involved in mucin-mediated immunomodulation, and metastasis, as well as the utility of mucins as targets for cancer immunotherapy and radioimmunotherapy.

• Publisher: Springer Nature B.V
• Subject: Antigen presentation / Antigens / Cancer / Cancer immunotherapy / Colonization / Cytolytic activity / Dendritic cells / Epitopes / Glycosylation / Homeostasis / Immunodominance / Immunomodulation / Immunosuppression / Immunotherapy / Leukocytes (neutrophilic) / Lymphocytes T / Macrophages / Major histocompatibility complex / Metastases / Metastasis / Mucin / Natural killer cells / Phenotypes / Toll-like receptors / Tumor cells