Immune Escape Mechanisms in Non Small Cell Lung Cancer

• Published in: Cancers Vol. 12; no. 12; p. 3605
• Main Authors: Anichini, Andrea, Perotti, Valentina E, Sgambelluri, Francesco, Mortarini, Roberta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.12.2020; MDPI
• Subjects: Adenocarcinoma; Antigen presentation; Chronic obstructive pulmonary disease; Cytokines; Cytotoxicity; DNA methylation; Gene expression; Heterozygosity; Histocompatibility antigen HLA; Hyperplasia; Immune checkpoint; Immune evasion; Immunotherapy; Invasiveness; Loss of heterozygosity; Lung cancer; Lymphocytes; Lymphocytes T; Morphology; Mutation; Neoantigens; Non-small cell lung carcinoma; Review; Small cell lung carcinoma; Solid tumors; Squamous cell carcinoma; Tumors; carcinoma in situ; immunotherapy; lung adenocarcinoma; HLA loss of heterozygosity; neoantigens; dysfunctional T cells; immune contexture; immune escape; pre-invasive lesions; lung squamous cell carcinoma; immune checkpoint blockade
• ISSN: 2072-6694; 2072-6694
• 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.