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Review
. 2020 Dec 2;12(12):3605.
doi: 10.3390/cancers12123605.

Immune Escape Mechanisms in Non Small Cell Lung Cancer

Andrea Anichini  1 , Valentina E Perotti  1 , Francesco Sgambelluri  1 , Roberta Mortarini  1
Affiliations
Review

Immune Escape Mechanisms in Non Small Cell Lung Cancer

Andrea Anichini et al. Cancers (Basel). .

Abstract

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.

Keywords: HLA loss of heterozygosity; carcinoma in situ; dysfunctional T cells; immune checkpoint blockade; immune contexture; immune escape; immunotherapy; lung adenocarcinoma; lung squamous cell carcinoma; neoantigens; pre-invasive lesions.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immune evolution in LUAD pre-invasive lesions. Changes in the indicated parameters along with progression of pre-invasive lesions to LUAD are shown by size and color of the shapes (larger vertical size and darker color: increase). NLT: normal lung tissue; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; LUAD: lung adenocarcinoma. The indicated evolution of CD8+ cells is according to reference [12], while other studies [10,11] report a different trend. Tregs: regulatory T cells; HLA-LOH: loss of heterozygosity at the HLA loci.
Figure 2
Figure 2
Immune evolution in LUSC pre-invasive lesions. Changes in the indicated parameters along with progression of pre-invasive lesions to LUAD are shown by size and color of the shapes (larger vertical size and darker color: increase). NBT: normal bronchial tissue; BCH: basal cell hyperplasia; SM: squamous metaplasia; DYS I–III: grade I–III dysplasia; CIS: carcinoma in situ; LUSC: lung squamous cell carcinoma. DCs: dendritic cells; TFH: T follicular helper cells; NK: natural killer cells.
See this image and copyright information in PMC

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