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.

摘要

唾液腺在口腔免疫中自然发挥着核心作用。唾液腺微环境不可避免地可能暴露于外源性因素，从而引发各种恶性和良性肿瘤的发生和形成。间充质干细胞被募集到唾液腺微环境中，与肿瘤细胞相互作用，并诱导抑制性细胞因子以及具有免疫抑制表型的细胞，例如髓源性抑制细胞 (MDSC) 和调节性 T 细胞 (Treg)。恶性和良性 SGT 中的免疫成分和肿瘤免疫反应仍在研究中。免疫反应可能直接在肿瘤生长和扩张中发挥限制作用，或者可能与其他细胞和调节分子合作参与形成丰富的肿瘤生长环境。免疫检查点分子（例如 PDL、HLA-G 和 LAG3) 经常在唾液腺微环境中的肿瘤细胞和/或肿瘤浸润淋巴细胞 (TIL) 上表达，它们表达的增加与 T 细胞耗竭、免疫耐受和肿瘤免疫逃逸有关。趋化因子和趋化因子受体对 SGT 的攻击行为有影响，因此它们可能成为癌症免疫治疗的候选靶点。为了广泛了解唾液腺，这篇综述首先简要介绍了正常唾液腺的免疫功能，然后通过关注间充质干细胞、免疫细胞亚群、免疫检查点分子、趋化因子和趋化因子描述了 SGT 的肿瘤微环境受体，最后介绍免疫检查点抑制剂以及癌症治疗的潜在靶点。HLA-G 和 LAG3) 经常在唾液腺微环境中的肿瘤细胞和/或肿瘤浸润淋巴细胞 (TIL) 上表达，它们表达的增加与 T 细胞耗竭、免疫耐受和肿瘤免疫逃逸有关。趋化因子和趋化因子受体对 SGT 的攻击行为有影响，因此它们可能成为癌症免疫治疗的候选靶点。为了广泛了解唾液腺，这篇综述首先简要介绍了正常唾液腺的免疫功能，然后通过关注间充质干细胞、免疫细胞亚群、免疫检查点分子、趋化因子和趋化因子描述了 SGT 的肿瘤微环境受体，最后介绍免疫检查点抑制剂以及癌症治疗的潜在靶点。HLA-G 和 LAG3) 经常在唾液腺微环境中的肿瘤细胞和/或肿瘤浸润淋巴细胞 (TIL) 上表达，它们表达的增加与 T 细胞耗竭、免疫耐受和肿瘤免疫逃逸有关。趋化因子和趋化因子受体对 SGT 的攻击行为有影响，因此它们可能成为癌症免疫治疗的候选靶点。为了广泛了解唾液腺，这篇综述首先简要介绍了正常唾液腺的免疫功能，然后通过关注间充质干细胞、免疫细胞亚群、免疫检查点分子、趋化因子和趋化因子描述了 SGT 的肿瘤微环境受体，最后介绍免疫检查点抑制剂以及癌症治疗的潜在靶点。