Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Front Immunol. 2019 Nov 28;10:2746. doi: 10.3389/fimmu.2019.02746. eCollection 2019.
For decades, cancer was considered a disease driven by genetic mutations in tumor cells, therefore afflicting a single cell type. This simplified view was slowly replaced by the understanding that interactions between malignant cells and neighboring stromal and immune cells-the tumor microenvironment (TME)-profoundly shape cancer progression. This understanding paved the way for an entirely new form of therapy that targets the immune cell compartment, which has revolutionized the treatment of cancer. In particular, agents activating T lymphocytes have become a key focus of these therapies, as they can induce durable responses in several cancer types. However, T cell targeting agents only benefit a fraction of patients. Thus, it is crucial to identify the roles of other immune cell types in the TME and understand how they influence T cell function and/or whether they present valuable therapeutic targets themselves. In this review, we focus on the myeloid compartment of the TME, a heterogeneous mix of cell types with diverse effector functions. We describe how distinct myeloid cell types can act as enemies of cancer cells by inducing or enhancing an existing immune response, while others act as strong allies, supporting tumor cells in their malignant growth and establishing an immune evasive TME. Specifically, we focus on the role of myeloid cells in the response and resistance to immunotherapy, and how modulating their numbers and/or state could provide alternative therapeutic entry-points.
几十年来，癌症被认为是由肿瘤细胞中的基因突变驱动的疾病，因此只影响单一细胞类型。这种简化的观点逐渐被另一种观点所取代，即恶性细胞与相邻的基质和免疫细胞（肿瘤微环境，TME）之间的相互作用深刻地影响着癌症的进展。这种认识为一种全新的针对免疫细胞的治疗方法铺平了道路，这种方法彻底改变了癌症的治疗方式。特别是，激活 T 淋巴细胞的药物已成为这些疗法的一个关键重点，因为它们可以在几种癌症类型中诱导持久的反应。然而，T 细胞靶向药物仅使一部分患者受益。因此，确定 TME 中其他免疫细胞类型的作用并了解它们如何影响 T 细胞功能，或者它们本身是否存在有价值的治疗靶点，这一点至关重要。在这篇综述中，我们重点介绍 TME 中的髓系细胞，这是一种具有不同效应功能的异质性细胞类型混合物。我们描述了不同的髓系细胞如何通过诱导或增强现有免疫反应来充当癌细胞的“敌人”，而另一些则充当强大的盟友，支持肿瘤细胞的恶性生长并建立免疫逃避的 TME。具体来说，我们重点关注髓系细胞在免疫治疗反应和耐药性中的作用，以及调节它们的数量和/或状态如何为替代治疗提供切入点。
