Mishra Alok K, Banday Shahid, Bharadwaj Ravi, Ali Amjad, Rashid Romana, Kulshreshtha Ankur, Malonia Sunil K
Department of Molecular, Cell and Cancer Biology, UMass Chan Medical School, Worcester, MA 01605, USA.
Department of Medicine, UMass Chan Medical School, Worcester, MA 01605, USA.
Vaccines (Basel). 2022 Dec 26;11(1):55. doi: 10.3390/vaccines11010055.
The revolution in cancer immunotherapy over the last few decades has resulted in a paradigm shift in the clinical care of cancer. Most of the cancer immunotherapeutic regimens approved so far have relied on modulating the adaptive immune system. In recent years, strategies and approaches targeting the components of innate immunity have become widely recognized for their efficacy in targeting solid cancers. Macrophages are effector cells of the innate immune system, which can play a crucial role in the generation of anti-tumor immunity through their ability to phagocytose cancer cells and present tumor antigens to the cells of adaptive immunity. However, the macrophages that are recruited to the tumor microenvironment predominantly play pro-tumorigenic roles. Several strategies targeting pro-tumorigenic functions and harnessing the anti-tumorigenic properties of macrophages have shown promising results in preclinical studies, and a few of them have also advanced to clinical trials. In this review, we present a comprehensive overview of the pathobiology of TAMs and their role in the progression of solid malignancies. We discuss various mechanisms through which TAMs promote tumor progression, such as inflammation, genomic instability, tumor growth, cancer stem cell formation, angiogenesis, EMT and metastasis, tissue remodeling, and immunosuppression, etc. In addition, we also discuss potential therapeutic strategies for targeting TAMs and explore how macrophages can be used as a tool for next-generation immunotherapy for the treatment of solid malignancies.
过去几十年来，癌症免疫疗法的革命已导致癌症临床护理的范式转变。到目前为止，大多数获批的癌症免疫治疗方案都依赖于调节适应性免疫系统。近年来，针对固有免疫成分的策略和方法因其在靶向实体癌方面的疗效而得到广泛认可。巨噬细胞是固有免疫系统的效应细胞，通过吞噬癌细胞并将肿瘤抗原呈递给适应性免疫细胞的能力，在抗肿瘤免疫的产生中发挥关键作用。然而，募集到肿瘤微环境中的巨噬细胞主要发挥促肿瘤作用。几种针对促肿瘤功能并利用巨噬细胞抗肿瘤特性的策略在临床前研究中已显示出有前景的结果，其中一些也已进入临床试验阶段。在这篇综述中，我们全面概述了肿瘤相关巨噬细胞的病理生物学及其在实体恶性肿瘤进展中的作用。我们讨论了肿瘤相关巨噬细胞促进肿瘤进展的各种机制，如炎症、基因组不稳定、肿瘤生长、癌症干细胞形成、血管生成、上皮-间质转化和转移、组织重塑以及免疫抑制等。此外，我们还讨论了靶向肿瘤相关巨噬细胞的潜在治疗策略，并探索巨噬细胞如何用作治疗实体恶性肿瘤的下一代免疫疗法的工具。
