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Cancer-associated mucins: role in immune modulation and metastasis

  • Rakesh Bhatia
  • Shailendra K. Gautam
  • Andrew Cannon
  • Christopher Thompson
  • Bradley R. Hall
  • Abhijit Aithal
  • Kasturi Banerjee
  • Maneesh Jain
  • Joyce C. Solheim
  • Sushil Kumar
  • Surinder K. BatraEmail author
NON-THEMATIC REVIEW

Abstract

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.

Keywords

Mucins Immunomodulation Cancer Inflammation Vaccine 

Notes

Grant support

This work was supported by funding from the National Institutes of Health (PO1 CA 217798, P50 CA127297, UO1 CA210240, UO1 CA200466, UO 1 CA213862, R21 CA223429, F30 CA225117, R01 CA183459, RO1 CA 195586, RO1 CA206444, R21 AA 026428, and RO1 CA228524).

Compliance with ethical standards

Conflicts of interest

SKB is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors have no potential conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Rakesh Bhatia
    • 1
  • Shailendra K. Gautam
    • 1
  • Andrew Cannon
    • 1
  • Christopher Thompson
    • 1
  • Bradley R. Hall
    • 2
  • Abhijit Aithal
    • 1
  • Kasturi Banerjee
    • 1
  • Maneesh Jain
    • 1
    • 3
  • Joyce C. Solheim
    • 4
  • Sushil Kumar
    • 1
  • Surinder K. Batra
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of SurgeryUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Fred and Pamela Buffett Cancer CenterUniversity of Nebraska Medical CenterOmahaUSA
  4. 4.Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmahaUSA

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