Immunological and biological dissection of normal and tumoral salivary glands

Abstract

Salivary glands naturally play central roles in oral immunity. The salivary glands microenvironment inevitable may be exposed to exogenous factors consequently triggering the initiation and formation of various malignant and benign tumors. Mesenchymal stem cells are recruited into salivary gland microenvironment, interact with tumor cells, and induce inhibitory cytokines as well as cells with immunosuppressive phenotypes such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). The immune components and tumor immune responses in malignant and benign SGTs are still under investigation. Immune responses may directly play a limiting role in tumor growth and expansion, or may participate in formation of a rich milieu for tumor growth in cooperation with other cellular and regulatory molecules. Immune checkpoint molecules (e.g. PDLs, HLA-G and LAG3) are frequently expressed on tumor cells and/or tumor-infiltrating lymphocytes (TILs) in salivary gland microenvironment, and an increase in their expression is associated with T cell exhaustion, immune tolerance and tumor immune escape. Chemokines and chemokine receptors have influential roles on aggressive behaviors of SGTs, and thereby they could be candidate targets for cancer immunotherapy. To present a broad knowledge on salivary glands, this review first provides a brief description on immunological functions of normal salivary glands, and then describe the SGT’s tumor microenvironment, by focusing on mesenchymal stem cells, immune cell subsets, immune checkpoint molecules, chemokines and chemokine receptors, and finally introduces immune checkpoint inhibitors as well as potential targets for cancer therapy.

Keywords:

• Salivary glands
• salivary gland tumors
• tumor microenvironment components
• immune system components
• mesenchymal stem cells
• immune checkpoint inhibitors

Conflict of interest statement

Authors state that there was no conflict of interest.

Additional information

Funding

This study was supported by a grant from Shiraz University of Medical Sciences, Shiraz, Iran (Grant number 21630 (99-01-106-23619). The study was approved by the local ethics committee of Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC.1399.866). The authors wish to thank Dr Seyed Mohammad Jafari (faculty member of English department at Shiraz University of Medical Sciences) for editing the manuscript and Mr. Ali Sefidbakht for his invaluable assistance in designing manuscript pictures.