法国巴黎大学的Jerome Galon研究组合作揭示了肺鳞癌早期产生过程中肿瘤在发生侵袭前就已经实现免疫逃逸。相关论文于2019年7月25日发表于国际著名学术期刊《自然》上。

研究人员发现免疫激活和免疫逃逸发生在肿瘤侵袭之前，并揭示了肺癌侵袭前阶段的相关免疫生物标志物。研究人员使用基因表达谱和多光谱成像分析了肺鳞癌发展过程中的9种形态阶段，这包括了来自于77个病人的122个标注明确的活检样品。研究人员确定了癌症和免疫途径的进化轨迹，包括(1)从正常组织到癌组织细胞增殖与DNA修复的增加；(2) 在低级别的侵袭前病变中，代谢和早期免疫感知通过激活常驻免疫细胞短暂地增加；(3) 在高级别侵袭前病变中，通过免疫检查点和抑制性白介素激活免疫反应和免疫逃逸；(4)肿瘤侵袭阶段EMT的激活。研究人员认为肺癌的发生与侵袭前支气管细胞和免疫反应的动态共同进化有关。这些发现强调了为早期检测开发免疫生物标志物以及为肺癌高危人群开发基于免疫治疗的化学预防方法的必要性。

据介绍，早发现并治疗对提高癌症患者的预后至关重要。了解癌症发生的生物学需要破译癌前病变的分子过程，并需要揭示癌症发展过程中决定病灶内免疫反应的因素。肿瘤内的适应性免疫反应已被证明在早期癌症中是最强的。

附：英文原文

Title: Immune evasion before tumour invasion in early lung squamous carcinogenesis

Author: Celine Mascaux, Mihaela Angelova, Angela Vasaturo, Jennifer Beane, Kahkeshan Hijazi, Geraldine Anthoine, Bndicte Buttard, Franoise Rothe, Karen Willard-Gallo, Annick Haller, Vincent Ninane, Arsne Burny, Jean-Paul Sculier, Avi Spira, Jerome Galon

Issue&Volume: Volume 571 Issue 7766

Abstract: 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. 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. 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 epithelialmesenchymal transition in the invasive stage of cancer. 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 chemopreventive approaches for individuals who are at high risk of developing lung cancer.

DOI: 10.1038/s41586-019-1330-0

Source: https://www.nature.com/articles/s41586-019-1330-0