Anichini Andrea, Perotti Valentina E, Sgambelluri Francesco, Mortarini Roberta
Human Tumors Immunobiology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
Cancers (Basel). 2020 Dec 2;12(12):3605. doi: 10.3390/cancers12123605.
Development of strong immune evasion has been traditionally associated with the late stages of solid tumor progression, since advanced cancers are more likely to have reached the third phase of the immunoediting process. However, by integrating a variety of approaches, evidence for active immune escape mechanisms has been found even in the pre-invasive lesions that later progress to the main NSCLC histotypes. Pre-invasive lesions of adenocarcinoma (LUAD) and of squamous cell carcinoma (LUSC) can show impaired antigen presentation, loss of heterozygosity at the Human Leukocyte Antigen (HLA) region, neoantigen silencing, activation of immune checkpoints, altered TH1/TH2 cytokine ratios, and immune contexture evolution. Analysis of large panels of LUAD vs. LUSC, of early stage NSCLC vs. normal lung tissue, of specific molecular subsets of NSCLC, and of distinct regions within the same tumor, indicates that all these processes of immune escape continue to evolve in the invasive stage of NSCLC, are associated with inter- and intra-tumor heterogeneity, and contribute to resistance to therapy by immune checkpoint blockade (ICB). In this review, we will discuss the most recent evidence on immune escape mechanisms developing from the precursor to invasive stage in NSCLC, and the contribution of immune evasion to resistance to ICB in lung cancer.
强大的免疫逃逸能力的发展传统上与实体瘤进展的晚期相关，因为晚期癌症更有可能已进入免疫编辑过程的第三阶段。然而，通过整合多种方法，即使在后来发展为主要非小细胞肺癌组织学类型的浸润前病变中也发现了主动免疫逃逸机制的证据。腺癌（LUAD）和鳞状细胞癌（LUSC）的浸润前病变可表现出抗原呈递受损、人类白细胞抗原（HLA）区域杂合性缺失、新抗原沉默、免疫检查点激活、TH1/TH2细胞因子比值改变以及免疫微环境演变。对大量LUAD与LUSC、早期非小细胞肺癌与正常肺组织、非小细胞肺癌的特定分子亚群以及同一肿瘤内不同区域的分析表明，所有这些免疫逃逸过程在非小细胞肺癌的浸润阶段继续演变，与肿瘤间和肿瘤内异质性相关，并导致对免疫检查点阻断（ICB）治疗的耐药性。在本综述中，我们将讨论关于非小细胞肺癌从癌前病变到浸润阶段免疫逃逸机制的最新证据，以及免疫逃逸对肺癌ICB耐药性的影响。
