The network of bidirectional homotypic and heterotypic interactions established among parenchymal tumour cells and surrounding mesenchymal stromal cells generates the tumour microenvironment (TME). These intricate crosstalks elicit both beneficial and adverse effects on tumour initiation and progression unbalancing the signals and responses from the neighbouring cells. Here, we highlight the structure, activities and evolution of TME cells considering a novel colorectal cancer (CRC) classification based on differential stromal composition and gene expression profiles. In this scenario, we scrutinise the molecular pathways that either change or become corrupted during CRC development and their relative prognostic value. Finally, we survey the therapeutic molecules directed against TME components currently available in clinical trials as well as those with stronger potential in preclinical studies. Elucidation of dynamic variations in the CRC TME cell composition and their relative contribution could provide novel diagnostic or prognostic biomarkers and allow more personalised therapeutic strategies.

中文翻译：

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是敌是友？大肠癌的肿瘤微环境困境。

在实质性肿瘤细胞与周围间充质基质细胞之间建立的双向同型和异型相互作用网络产生了肿瘤微环境（TME）。这些错综复杂的串扰对肿瘤的发生和发展都产生了有利和不利的影响，使邻近细胞的信号和反应失去了平衡。在这里，我们考虑到基于不同基质成分和基因表达谱的新型结直肠癌（CRC）分类，突出了TME细胞的结构，活性和进化。在这种情况下，我们研究了在CRC发生过程中改变或破坏的分子途径及其相对预后价值。最后，我们调查了针对TME组分的治疗分子，这些分子目前在临床试验中以及在临床前研究中具有更强潜力的分子。阐明CRC TME细胞组成中的动态变化及其相对作用可以提供新颖的诊断或预后生物标志物，并允许采用更具个性化的治疗策略。