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纳米医学重塑肿瘤微环境用于实体瘤免疫治疗。

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy.

机构信息

Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai 200331, P. R. China.

Shanghai Institute of Ceramics, Chinese Academy of Sciences; Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai 200050, P. R. China.

出版信息

J Am Chem Soc. 2024 Apr 17;146(15):10217-10233. doi: 10.1021/jacs.3c14005. Epub 2024 Apr 2.

Abstract

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.

摘要

虽然免疫疗法在治疗血液恶性肿瘤方面相对有效,但目前其治疗实体瘤的疗效仍不理想甚至无效。与血液癌症相比,实体瘤表现出截然不同的免疫抑制微环境,严重降低了免疫疗法的疗效:(1)缺氧和轻度酸性等化学特征抑制免疫细胞的活性,(2)肿瘤微环境中免疫细胞的促瘤驯化进一步削弱了免疫疗法的效果,(3)实体肿瘤组织致密的物理屏障阻止了活性免疫细胞的有效肿瘤内浸润和接触杀伤。因此,我们认为逆转免疫抑制微环境对于实体瘤的免疫治疗至关重要。由于具有独特的形态、结构和组成,纳米药物已成为实现这一目标的有力工具。在本观点中,我们将首先简要介绍实体瘤的免疫抑制微环境,然后全面总结基于纳米医学的实体瘤免疫治疗的最新进展,重塑肿瘤免疫微环境。我们高度期望本观点将有助于推进实体瘤的免疫治疗,并且对这一新兴领域的未来发展充满乐观。

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