Thyagarajan Anita, Alshehri Mamdouh Salman A, Miller Kelly L R, Sherwin Catherine M, Travers Jeffrey B, Sahu Ravi P
Department of Pharmacology and Toxicology, Boonshoft School of Medicine Wright State University, Dayton, OH 45435, USA.
Department of Pharmacology and Toxicology, Pharmacy College, Taibah University, Medina 42353, Saudi Arabia.
Cancers (Basel). 2019 Oct 24;11(11):1627. doi: 10.3390/cancers11111627.
Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC.
胰腺导管腺癌（PDAC）仍然是一种具有毁灭性的人类恶性肿瘤，预后较差，生存率较低。几种细胞机制与胰腺癌的发生有关，也与诱导肿瘤对已知治疗方案产生耐药性有关。在各种因素中，免疫逃逸机制在肿瘤进展以及阻碍包括PDAC在内的癌症治疗疗效方面起着关键作用。在免疫抑制细胞类型中，髓源性抑制细胞（MDSCs）已得到广泛研究，并证明其不仅支持PDAC的发展，还会阻碍治疗药物引发的抗肿瘤免疫反应。值得注意的是，最近人们致力于设计针对MDSCs的新方法以限制其作用。在PDAC的临床前和临床环境中，已经探索了多种策略，包括基于免疫的方法，单独或与治疗药物联合使用以靶向MDSCs。本综述重点介绍了MDSCs的作用和机制，以及这种免疫调节细胞类型作为提高PDAC治疗方案疗效的潜在靶点的意义。
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