SCI
1July
Immune evasion before tumour invasion in early lung squamous carcinogenesis
Mascaux Céline,Angelova Mihaela,Vasaturo Angela et al. Immune evasion before tumour invasion in early lung squamous carcinogenesis.[J] .Nature, , undefined: undefined.
Early detection and treatment are critical for improving the outcome of patients with cancer. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development.
早期发现和治疗对于改善癌症患者的预后至关重要。了解癌症发生的大部分未知生物学需要解读癌前病变中的分子过程，并揭示癌症发展过程中病灶内免疫反应的决定因素。
The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma. Here we show that immune activation and immune escape occur before tumour invasion, and reveal the relevant immune biomarkers of the pre-invasive stages of carcinogenesis in the lung. We used gene-expression profiling and multispectral imaging to analyse a dataset of 9 morphological stages of the development of lung squamous cell carcinoma, which includes 122 well-annotated biopsies from 77 patients.
先前已经证明肿瘤内的适应性免疫应答在癌的最早阶段是最强的。在这里，我们显示免疫激活和免疫逃逸发生在肿瘤入侵之前，并揭示肺癌发生的侵入前阶段的相关免疫生物标志物。我们使用基因表达谱和多光谱成像来分析肺鳞状细胞癌发展的9个形态阶段的数据集，其中包括来自77个患者的122个新鲜的活组织检查。
We identified evolutionary trajectories of cancer and immune pathways that comprise (1) a linear increase in proliferation and DNA repair from normal to cancerous tissue; (2) a transitory increase of metabolism and early immune sensing, through the activation of resident immune cells, in low-grade pre-invasive lesions; (3) the activation of immune responses and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, (4) the activation of the epithelial–mesenchymal transition in the invasive stage of cancer.
我们确定了癌症和免疫途径的进化轨迹，包括（1）从正常到癌组织的增殖和DNA修复的线性增加; （2）通过激活常驻免疫细胞，在低度侵袭性病变中，代谢和早期免疫感知的短暂增加; （3）通过免疫检查点激活免疫反应和免疫逃逸，以及来自高级侵袭前病变的抑制性白细胞介素;最后，（4）癌症侵袭阶段的上皮 - 间质转化的激活。
We propose that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection as well as immunotherapy based chemo preventive approaches for individuals who are at high risk of developing lung cancer.
我们提出肺癌发生涉及入侵前支气管细胞和免疫反应的动态共同进化。这些研究结果强调了开发用于早期检测的免疫生物标志物以及基于免疫疗法的化学预防方法的需要，这些方法适用于患肺癌高风险的个体。
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