BACKGROUND Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1-C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs). METHODS Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs. RESULTS Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-β dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways. CONCLUSIONS The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.

中文翻译：

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大肠癌中免疫亚型和共有分子亚型之间的相关性鉴定了新的肿瘤微环境特征，具有预后和治疗意义。

背景技术实体瘤的生长是癌细胞与其微环境之间复杂相互作用的结果。最近，对实体瘤进行了新的全球转录组免疫分类，已鉴定出六种免疫亚型（ISs）（C1-C6）。我们的目的是明确表征结直肠癌（CRC）中的IS，并评估其与共有分子亚型（CMS）的相互作用。方法临床和分子信息，包括CMS和IS，均获自The Cancer Genome Atlas（TCGA）（N = 625）。通过使用CMS，进行了免疫细胞群体，差异基因表达和基因集富集分析，以表征全球CRC群体中的IS。结果在CRC中仅鉴定出5个IS，主要是C1伤口愈合（77％）和C2IFN-γ显性（17％）。CMS1显示最高的C2比例（53％），而C1在CMS2中尤为突出（91％）。CMS3具有最高的C3炎性（7％）和C4淋巴细胞耗竭的ISs（4％）代表，而所有C6TGF-β显性病例均属于CMS4（2.3％）。IS在CRC中的预后相关性与全球TCGA的报道存在显着差异，并且IS对CRC患者的预后进行分层的能力要强于CMS分类。C2具有较高密度的CD8，CD4激活的滤泡辅助性T细胞，调节性T细胞和嗜中性粒细胞，并且M1 / M2极化度最高。C2具有增强的与免疫系统，细胞凋亡和DNA修复，mTOR信号传导和氧化磷酸化有关的途径的激活，而C1更依赖于代谢途径。