基于髓源性抑制细胞的食药用菌多糖抗肿瘤免疫作用机制

Edible and medicinal fungal polysaccharides inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSCs) on cancers

摘要:

髓源性抑制细胞(myeloid-derived suppressor cells，MDSCs)是一种异质性的免疫调节细胞。在癌症机体中，MDSCs是主要的免疫抑制细胞，通过多种途径诱导T淋巴细胞衰竭和凋亡，促进肿瘤细胞逃逸，从而导致肿瘤不受控制地生长，是癌症治疗的主要障碍。目前，MDSCs是癌症药物研究的热点和关键靶点。近年来，研究报道显示多糖可下调MDSCs在癌症患者及肿瘤实验动物体内数量和比例，并诱导免疫抑制功能丧失。食药用菌多糖是天然多糖的主要来源，可以通过多种途径激活肿瘤免疫应答，其抑制MDSCs功能的研究报道逐年增多，目前研究主要集中在香菇多糖、灵芝多糖等部分种类。因此，本文简要描述髓源性抑制细胞在癌症中的免疫抑制功能，然后详细地综述食药用菌多糖对髓源性抑制细胞作用的研究进展，以期为食药用菌多糖在肿瘤免疫药物开发及辅助增强(如免疫检查点抑制剂)等免疫治疗提供新思路。

Abstract:

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immunomodulatory cells. In the instance of cancers, they exert immunosuppressive functions. To be specific, they induce T cell exhaustion and apoptosis through multiple pathways to promote the escape of tumor cells from destruction by the immune system and sustain cancer progression. Thus, they are the main obstacle in the fight against cancers. At the moment, MDSCs are the focus in development of anti-cancer drugs and the key targets of the drugs. It has been reported that polysaccharides reduced the count and proportion of MDSCs in cancer patients and tumor-bearing mice and eliminate the immunosuppression. Natural edible and medicinal fungal polysaccharides can activate immune response to tumors through multiple pathways, and there has been an explosion of research on the suppression of the immunosuppressive function of MDSCs. The currently available studies mainly focus on polysaccharides from Lentinula edodes and Ganoderma lucidum. In this review, we briefed the immunosuppressive mechanism of MDSCs in the cases of cancers, and then summarized the effects of edible and medicinal fungal polysaccharides on MDSCs, hoping to provide a new mindset for the development of anti-tumor drugs and auxiliary enhancement of immunotherapy such as immune checkpoint inhibitors with edible and medicinal fungal polysaccharides.