Goswami Sangeeta, Anandhan Swetha, Raychaudhuri Deblina, Sharma Padmanee
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nat Rev Immunol. 2023 Feb;23(2):106-120. doi: 10.1038/s41577-022-00737-w. Epub 2022 Jun 13.
Myeloid cells are the most abundant immune components of the tumour microenvironment, where they have a variety of functions, ranging from immunosuppressive to immunostimulatory roles. The myeloid cell compartment comprises many different cell types, including monocytes, macrophages, dendritic cells and granulocytes, that are highly plastic and can differentiate into diverse phenotypes depending on cues received from their microenvironment. In the past few decades, we have gained a better appreciation of the complexity of myeloid cell subsets and how they are involved in tumour progression and resistance to cancer therapies, including immunotherapy. In this Review, we highlight key features of monocyte and macrophage biology that are being explored as potential targets for cancer therapies and what aspects of myeloid cells need a deeper understanding to identify rational combinatorial strategies to improve clinical outcomes of patients with cancer. We discuss therapies that aim to modulate the functional activities of myeloid cell populations, impacting their recruitment, survival and activity in the tumour microenvironment, acting at the level of cell surface receptors, signalling pathways, epigenetic machinery and metabolic regulators. We also describe advances in the development of genetically engineered myeloid cells for cancer therapy.
髓系细胞是肿瘤微环境中最丰富的免疫成分，在肿瘤微环境中它们具有多种功能，从免疫抑制作用到免疫刺激作用不等。髓系细胞区室包含许多不同的细胞类型，包括单核细胞、巨噬细胞、树突状细胞和粒细胞，这些细胞具有高度可塑性，可根据从其微环境接收到的信号分化为不同的表型。在过去几十年中，我们对髓系细胞亚群的复杂性以及它们如何参与肿瘤进展和对癌症治疗（包括免疫治疗）的抗性有了更好的认识。在本综述中，我们重点介绍了正在作为癌症治疗潜在靶点进行探索的单核细胞和巨噬细胞生物学的关键特征，以及髓系细胞的哪些方面需要更深入的了解，以确定合理的联合策略来改善癌症患者的临床结局。我们讨论了旨在调节髓系细胞群体功能活性的疗法，这些疗法会影响它们在肿瘤微环境中的募集、存活和活性，作用于细胞表面受体、信号通路、表观遗传机制和代谢调节因子水平。我们还描述了用于癌症治疗的基因工程髓系细胞开发方面的进展。
