Saeed Madiha, Chen Fangming, Ye Jiayi, Shi Yang, Lammers Twan, De Geest Bruno G, Xu Zhi Ping, Yu Haijun
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
Adv Mater. 2021 Jul;33(30):e2008094. doi: 10.1002/adma.202008094. Epub 2021 May 28.
The tumor immune microenvironment (TIME) is comprised of a complex milieu that contributes to stunting antitumor immune responses by restricting T cells to accumulate in the vicinity of the tumor. Nanomedicine-based strategies are being proposed as a salvage effort to reinvigorate antitumor immunity. Various strategies, however, often fail to unleash the antitumor immune response because of the paucity of appropriate therapeutic targets in the complex TIME, invigorating a fervor of investigation into mechanisms underlying the TIME to resist nanomedicines. In this review article, effective nano/biomaterial-based delivery and TIME normalization approaches that promote T cell-mediated antitumor immune response will be discussed, with a focus on emerging preclinical and clinical strategies for immune normalization. Based on currently available evidence, it seems as if the ultimate success of cancer immunotherapy and nanomedicine hinges on the capacity to normalize the TIME. Here, how nanomedicines target immunosuppressive cells and signaling pathways to broaden the impact of cancer immunotherapy are explored. Acquisition of the urgently needed knowledge of nanomedicine-mediated immune normalization will guide researchers and scientists towards clinical applications of cancer immunotherapy.
肿瘤免疫微环境（TIME）由一个复杂的环境组成，该环境通过限制T细胞在肿瘤附近积聚来阻碍抗肿瘤免疫反应。基于纳米医学的策略正被作为一种挽救措施提出，以重振抗肿瘤免疫力。然而，由于复杂的肿瘤免疫微环境中缺乏合适的治疗靶点，各种策略往往无法释放抗肿瘤免疫反应，这激发了人们对肿瘤免疫微环境抵抗纳米药物的潜在机制进行深入研究的热情。在这篇综述文章中，我们将讨论基于纳米/生物材料的有效递送和肿瘤免疫微环境正常化方法，这些方法可促进T细胞介导的抗肿瘤免疫反应，重点关注新兴的免疫正常化临床前和临床策略。根据目前可得的证据，癌症免疫疗法和纳米医学的最终成功似乎取决于使肿瘤免疫微环境正常化的能力。在此，我们探讨纳米药物如何靶向免疫抑制细胞和信号通路以扩大癌症免疫疗法的影响。获取纳米医学介导的免疫正常化这一急需的知识将引导研究人员和科学家走向癌症免疫疗法的临床应用。
