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纳米颗粒在肿瘤微环境重塑中改善癌症免疫治疗的潜在应用。

Potential applications of nanoparticles for tumor microenvironment remodeling to ameliorate cancer immunotherapy.

机构信息

Extrathoracic and Thyroid Mammary Surgery, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China.

Encephalopathy Center, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China.

出版信息

Int J Pharm. 2019 Oct 30;570:118636. doi: 10.1016/j.ijpharm.2019.118636. Epub 2019 Aug 22.

Abstract

In recent years, researchers have made significant innovations in the field of tumor immunotherapy based on the knowledge of biology, oncology, and immunology. Tumor immunotherapy involves the use of immune checkpoint inhibitors and CAR (chimeric antigen receptor)-T cell therapy. As compared with conventional chemotherapy, immunotherapy is a potential approach to induce a more powerful immune response against tumor in the patient suffering from the advanced stage malignancy. Regardless of the developments made, a large number of clinical studies have confirmed that a substantial number of cancer patients still demonstrate non-responsiveness to immunotherapy, mainly due to the immunomodulating interactions of tumor cells with the immunosuppressive tumor microenvironment (iTME). It leads to immune tolerance of tumors and influences the efficacy of immunotherapy. This immune failure could be attributed to a complex immunosuppressive network comprising stromal and inflammatory cells, vessel system, ECM (extracellular matrix) and the cytokines released in tumor microenvironment (TME). The antitumor immune activity can be enhanced at different stages of tumor development by selective suppression of inhibitory pathways in the TME. This specific task can be achieved by using nano-sized drug delivery tools which are specific in their action and biocompatible in nature. Several recent studies have described the use of nanoparticles for iTME remodeling through the specific elimination of immunosuppressive cells, obstructing immune checkpoints, promotion of inflammatory cytokines, and amending the regulatory cells of the immune system. The efficacy of current immunotherapy can be improved by nanoparticle-mediated remodeling of iTME.

摘要

近年来,研究人员在生物学、肿瘤学和免疫学知识的基础上,在肿瘤免疫治疗领域取得了重大创新。肿瘤免疫治疗涉及免疫检查点抑制剂和 CAR(嵌合抗原受体)-T 细胞疗法的应用。与传统化疗相比,免疫疗法是一种在晚期恶性肿瘤患者中诱导更强大免疫反应的潜在方法。无论取得了哪些进展,大量的临床研究都证实,大量癌症患者对免疫疗法仍然没有反应,主要是由于肿瘤细胞与免疫抑制性肿瘤微环境(iTME)的免疫调节相互作用。这导致肿瘤的免疫耐受,并影响免疫疗法的疗效。这种免疫失败可能归因于一个复杂的免疫抑制网络,包括基质和炎症细胞、血管系统、细胞外基质(ECM)和肿瘤微环境(TME)中释放的细胞因子。通过选择性抑制 TME 中的抑制性途径,可以在肿瘤发展的不同阶段增强抗肿瘤免疫活性。这一特定任务可以通过使用具有特定作用和生物相容性的纳米级药物输送工具来实现。最近的几项研究描述了通过特异性消除免疫抑制细胞、阻断免疫检查点、促进炎症细胞因子以及修正免疫系统的调节细胞来利用纳米颗粒进行 iTME 重塑。通过纳米颗粒介导的 iTME 重塑可以提高当前免疫疗法的疗效。

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