Beach Callum, MacLean David, Majorova Dominika, Arnold James N, Olcina Monica M
Department of Oncology, Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
Front Oncol. 2022 Sep 29;12:1020606. doi: 10.3389/fonc.2022.1020606. eCollection 2022.
The efficacy of radiotherapy, a mainstay of cancer treatment, is strongly influenced by both cellular and non-cellular features of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a heterogeneous population within the TME and their prevalence significantly correlates with patient prognosis in a range of cancers. Macrophages display intrinsic radio-resistance and radiotherapy can influence TAM recruitment and phenotype. However, whether radiotherapy alone can effectively "reprogram" TAMs to display anti-tumor phenotypes appears conflicting. Here, we discuss the effect of radiation on macrophage recruitment and plasticity in cancer, while emphasizing the role of specific TME components which may compromise the tumor response to radiation and influence macrophage function. In particular, this review will focus on soluble factors (cytokines, chemokines and components of the complement system) as well as physical changes to the TME. Since the macrophage response has the potential to influence radiotherapy outcomes this population may represent a drug target for improving treatment. An enhanced understanding of components of the TME impacting radiation-induced TAM recruitment and function may help consider the scope for future therapeutic avenues to target this plastic and pervasive population.
放射疗法作为癌症治疗的主要手段，其疗效受到肿瘤微环境（TME）的细胞和非细胞特征的强烈影响。肿瘤相关巨噬细胞（TAM）是TME中的异质群体，其在多种癌症中的普遍存在与患者预后显著相关。巨噬细胞表现出内在的放射抗性，放射疗法可影响TAM的募集和表型。然而，单纯放疗是否能有效地“重编程”TAM以呈现抗肿瘤表型，这一点似乎存在争议。在此，我们讨论辐射对癌症中巨噬细胞募集和可塑性的影响，同时强调特定TME成分的作用，这些成分可能会损害肿瘤对辐射的反应并影响巨噬细胞功能。特别是，本综述将聚焦于可溶性因子（细胞因子、趋化因子和补体系统成分）以及TME的物理变化。由于巨噬细胞反应有可能影响放疗结果，这一群体可能成为改善治疗的药物靶点。增强对影响辐射诱导的TAM募集和功能的TME成分的理解，可能有助于考虑未来针对这一可塑性且普遍存在的群体的治疗途径的范围。
