Immune surveillance in clinical regression of preinvasive squamous cell lung cancer. - GreenMedInfo Summary
Immune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Cancer.
Cancer Discov. 2020 Oct ;10(10):1489-1499. Epub 2020 Jul 20. PMID: 32690541
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 carcinomalesions 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,signaling is upregulated, and the immunomodulatoris downregulated. Changes appear intrinsic to the carcinomalesions, 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...