Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Cancer Immunol Immunother. 2019 Nov;68(11):1819-1829. doi: 10.1007/s00262-018-02296-3. Epub 2019 Jan 3.
At present, significant experimental and clinical data confirm the active involvement of the peripheral nervous system (PNS) in different phases of cancer development and progression. Most of the research effort focuses on the impact of distinct neuronal types, e.g., adrenergic, cholinergic, dopaminergic, etc. in carcinogenesis, generally ignoring neuroglia. The very fact that these cells far outnumber the other cellular types may also play an important role worthy of study in this context. The most prevalent neuroglia within the PNS consists of Schwann cells (SCs). These cells play a substantial role in maintaining homeostasis within the nervous system. They possess distinct immunomodulatory, inflammatory and regenerative capacities-also, one should consider their broad distribution throughout the body; this makes them a perfect target for malignant cells during the initial stages of cancer development and the very formation of the tumor microenvironment itself. We show that SCs in the tumor milieu attract different subsets of immune regulators and augment their ability to suppress effector T cells. SCs may also up-regulate invasiveness of tumor cells and support metastatic disease. We outline the interactive potential of SCs juxtaposed with cancerous cells, referring to data from various external sources alongside data of our own.
目前,大量的实验和临床数据证实了周围神经系统(PNS)在癌症发展和进展的不同阶段的积极参与。大多数研究都集中在不同神经元类型的影响上,例如肾上腺素能、胆碱能、多巴胺能等,在致癌作用中,通常忽略了神经胶质。事实上,这些细胞的数量远远超过其他细胞类型,这在这种情况下也可能具有重要的研究价值。PNS 中最常见的神经胶质是雪旺细胞(SCs)。这些细胞在维持神经系统内的稳态中起着重要的作用。它们具有独特的免疫调节、炎症和再生能力,也应该考虑到它们在全身的广泛分布;这使得它们在癌症发展的早期阶段和肿瘤微环境本身的形成过程中成为恶性细胞的完美靶标。我们表明,肿瘤微环境中的SCs 吸引了不同的免疫调节剂亚群,并增强了它们抑制效应 T 细胞的能力。SCs 还可能上调肿瘤细胞的侵袭性并支持转移性疾病。我们概述了与癌细胞并列的SCs 的相互作用潜力,同时参考了来自不同外部来源的数据和我们自己的数据。