<p>Details of molecular investigations performed on each sample. Clinical and outcome data is also presented. In all cases with a previous history of lung cancer, this was of squamous histology.</p>
<div>Abstract<p>Before squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such lesions become cancer, whereas a third spontaneously regress. Although recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of precancerous lesions remain unknown. Here, we show that host immune surveillance is strongly implicated in lesion regression. Using bronchoscopic biopsies from human subjects, we find that regressive carcinoma <i>in situ</i> lesions harbor more infiltrating immune cells than those that progress to cancer. Moreover, molecular profiling of these lesions identifies potential immune escape mechanisms specifically in those that progress to cancer: antigen presentation is impaired by genomic and epigenetic changes, <i>CCL27–CCR10</i> signaling is upregulated, and the immunomodulator <i>TNFSF9</i> is downregulated. Changes appear intrinsic to the carcinoma <i>in situ</i> lesions, as the adjacent stroma of progressive and regressive lesions are transcriptomically similar.</p>Significance:<p>Immune evasion is a hallmark of cancer. For the first time, this study identifies mechanisms by which precancerous lesions evade immune detection during the earliest stages of carcinogenesis and forms a basis for new therapeutic strategies that treat or prevent early-stage lung cancer.</p><p><i>See related commentary by Krysan et al., p. 1442</i>.</p><p><i>This article is highlighted in the In This Issue feature, p. 1426</i></p></div>
<p>Immune cell deconvolution from molecular data. Relative proportions of immune cell subtypes are predicted from gene expression data using the Danaher method, and from methylation data using methylCIBERSORT. Differences between progressive and regressive groups are reported here.</p>
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