Akins Erin A, Aghi Manish K, Kumar Sanjay
University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Berkeley, CA 94720, USA.
Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
iScience. 2020 Nov 5;23(12):101770. doi: 10.1016/j.isci.2020.101770. eCollection 2020 Dec 18.
Tumor progression is profoundly influenced by interactions between cancer cells and the tumor microenvironment (TME). Among the various non-neoplastic cells present, immune cells are critical players in tumor development and have thus emerged as attractive therapeutic targets. Malignant gliomas exhibit a unique immune landscape characterized by high numbers of tumor-associated macrophages (TAMs). Despite encouraging preclinical results, targeting TAMs has yielded limited clinical success as a strategy for slowing glioma progression. The slow translational progress of TAM-targeted therapies is due in part to an incomplete understanding of the factors driving TAM recruitment, differentiation, and polarization. Furthermore, the functions that TAMs adopt in gliomas remain largely unknown. Progress in addressing these gaps requires sophisticated culture platforms capable of capturing key cellular and physical TME features. This review summarizes the current understanding of TAMs in gliomas and highlights the utility of TME models for investigating TAM-cancer cell cross talk.
肿瘤进展受到癌细胞与肿瘤微环境(TME)之间相互作用的深刻影响。在存在的各种非肿瘤细胞中,免疫细胞是肿瘤发展的关键参与者,因此已成为有吸引力的治疗靶点。恶性胶质瘤呈现出独特的免疫格局,其特征是大量肿瘤相关巨噬细胞(TAM)。尽管临床前结果令人鼓舞,但作为减缓胶质瘤进展的策略,靶向TAM的临床成功率有限。TAM靶向治疗的转化进展缓慢,部分原因是对驱动TAM募集、分化和极化的因素了解不全面。此外,TAM在胶质瘤中所发挥的功能在很大程度上仍然未知。解决这些差距需要能够捕捉关键细胞和物理TME特征的复杂培养平台。本综述总结了目前对胶质瘤中TAM的理解,并强调了TME模型在研究TAM与癌细胞相互作用方面的效用。