Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
Department of Biochemistry and Molecular Pharmacology, New York University (NYU) Langone Medical Center, New York, NY, United States.
Front Immunol. 2023 Oct 23;14:1275890. doi: 10.3389/fimmu.2023.1275890. eCollection 2023.
The growth and metastasis of solid tumours is known to be facilitated by the tumour microenvironment (TME), which is composed of a highly diverse collection of cell types that interact and communicate with one another extensively. Many of these interactions involve the immune cell population within the TME, referred to as the tumour immune microenvironment (TIME). These non-cell autonomous interactions exert substantial influence over cell behaviour and contribute to the reprogramming of immune and stromal cells into numerous pro-tumourigenic phenotypes. The study of some of these interactions, such as the PD-1/PD-L1 axis that induces CD8 T cell exhaustion, has led to the development of breakthrough therapeutic advances. Yet many common analyses of the TME either do not retain the spatial data necessary to assess cell-cell interactions, or interrogate few (<10) markers, limiting the capacity for cell phenotyping. Recently developed digital pathology technologies, together with sophisticated bioimage analysis programs, now enable the high-resolution, highly-multiplexed analysis of diverse immune and stromal cell markers within the TME of clinical specimens. In this article, we review the tumour-promoting non-cell autonomous interactions in the TME and their impact on tumour behaviour. We additionally survey commonly used image analysis programs and highly-multiplexed spatial imaging technologies, and we discuss their relative advantages and limitations. The spatial organization of the TME varies enormously between patients, and so leveraging these technologies in future studies to further characterize how non-cell autonomous interactions impact tumour behaviour may inform the personalization of cancer treatment..
肿瘤的生长和转移被认为是由肿瘤微环境(TME)促进的,TME 由高度多样化的细胞类型组成,这些细胞类型之间广泛地相互作用和交流。这些相互作用中的许多涉及到 TME 中的免疫细胞群体,称为肿瘤免疫微环境(TIME)。这些非细胞自主的相互作用对细胞行为产生了巨大的影响,并促使免疫细胞和基质细胞重新编程为许多促进肿瘤发生的表型。对这些相互作用中的一些的研究,例如诱导 CD8 T 细胞耗竭的 PD-1/PD-L1 轴,已经导致了突破性的治疗进展。然而,TME 的许多常见分析要么没有保留评估细胞-细胞相互作用所必需的空间数据,要么只检测很少的(<10)标志物,限制了细胞表型分析的能力。最近开发的数字病理学技术,加上复杂的生物图像分析程序,现在可以在临床标本的 TME 中对多样化的免疫和基质细胞标志物进行高分辨率、高度多重化的分析。在本文中,我们回顾了 TME 中促进肿瘤的非细胞自主相互作用及其对肿瘤行为的影响。我们还调查了常用的图像分析程序和高度多重化的空间成像技术,并讨论了它们的相对优势和局限性。TME 的空间组织在患者之间差异巨大,因此在未来的研究中利用这些技术来进一步描述非细胞自主相互作用如何影响肿瘤行为,可能有助于癌症治疗的个体化。
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