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Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.

ABSTRACT: 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 in situ 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, CCL27-CCR10 signaling is upregulated, and the immunomodulator TNFSF9 is downregulated. Changes appear intrinsic to the carcinoma in situ lesions, as the adjacent stroma of progressive and regressive lesions are transcriptomically similar. SIGNIFICANCE: 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.See related commentary by Krysan et al., p. 1442.This article is highlighted in the In This Issue feature, p. 1426.

SUBMITTER: Pennycuick A

PROVIDER: S-EPMC7611527 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.

Pennycuick Adam A Teixeira Vitor H VH AbdulJabbar Khalid K Raza Shan E Ahmed SEA Lund Tom T Akarca Ayse U AU Rosenthal Rachel R Kalinke Lukas L Chandrasekharan Deepak P DP Pipinikas Christodoulos P CP Lee-Six Henry H Hynds Robert E RE Gowers Kate H C KHC Henry Jake Y JY Millar Fraser R FR Hagos Yeman B YB Denais Celine C Falzon Mary M Moore David A DA Antoniou Sophia S Durrenberger Pascal F PF Furness Andrew J AJ Carroll Bernadette B Marceaux Claire C Asselin-Labat Marie-Liesse ML Larson William W Betts Courtney C Coussens Lisa M LM Thakrar Ricky M RM George Jeremy J Swanton Charles C Thirlwell Christina C Campbell Peter J PJ Marafioti Teresa T Yuan Yinyin Y Quezada Sergio A SA McGranahan Nicholas N Janes Sam M SM

Cancer discovery 20200720 10

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. Usi ...[more]

PMID: 32690541

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Dataset Information

Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.

Publications

Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.

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