Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis
Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis
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DOI：
10.1038/s41416-020-0881-z
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发表时间：
2020-05-18
影响因子：
8.8
通讯作者：
Verhoef, Cornelis
中科院分区：
文献类型：
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作者：
Hoppener, Diederik J.;Nierop, Pieter M. H.;Verhoef, Cornelis
背景：仅表现促结缔组织病理性生长模式(DHGP)的切除结直肠癌肝转移(CRLM)患者的生存率高于任何非促结缔组织增生性疾病(非dHGP)患者。本研究的目的是比较dHGP和非dHGP的肿瘤微环境。方法对3组化疗初期接受CRLM手术的患者的肿瘤微环境进行研究。A组采用半定量免疫组织化学方法，B组采用免疫组织化学和数字图像分析方法对瘤内和瘤周T细胞进行计数，C组采用流式细胞仪测定各T细胞亚群的相对比例。结果A、B、C队列中分别有117、34、79例患者，dHGP发生率分别为27%、29%、15%。A组和B组分别显示瘤周和瘤内的细胞毒性CD8+T细胞在dHGP中的浓缩，以及较高的CD8+/CD4+比率(A组)。对C组新鲜肿瘤组织的流式细胞仪分析证实了这些结果；dHGP与CD8+升高和CD4+T细胞亚群降低相关，导致CD8+/CD4+比值升高。结论dHGP患者的肿瘤微环境具有明显的细胞毒免疫浸润性增加的特点，为其较好的生存提供了潜在的解释。
Background Patients with resected colorectal liver metastasis (CRLM) who display only the desmoplastic histopathological growth pattern (dHGP) exhibit superior survival compared to patients with any non-desmoplastic growth (non-dHGP). The aim of this study was to compare the tumour microenvironment between dHGP and non-dHGP. Methods The tumour microenvironment was investigated in three cohorts of chemo-naive patients surgically treated for CRLM. In cohort A semi-quantitative immunohistochemistry was performed, in cohort B intratumoural and peritumoural T cells were counted using immunohistochemistry and digital image analysis, and in cohort C the relative proportions of individual T cell subsets were determined by flow cytometry. Results One hundred and seventeen, 34, and 79 patients were included in cohorts A, B, and C, with dHGP being observed in 27%, 29%, and 15% of patients, respectively. Cohorts A and B independently demonstrated peritumoural and intratumoural enrichment of cytotoxic CD8+ T cells in dHGP, as well as a higher CD8+/CD4+ ratio (cohort A). Flow cytometric analysis of fresh tumour tissues in cohort C confirmed these results; dHGP was associated with higher CD8+ and lower CD4+ T cell subsets, resulting in a higher CD8+/CD4+ ratio. Conclusion The tumour microenvironment of patients with dHGP is characterised by an increased and distinctly cytotoxic immune infiltrate, providing a potential explanation for their superior survival.