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Genetic and immunologic features of recurrent stage I lung adenocarcinoma.

ABSTRACT: Although surgery for early-stage lung cancer offers the best chance of cure, recurrence still occurs between 30 and 50% of the time. Why patients frequently recur after complete resection of early-stage lung cancer remains unclear. Using a large cohort of stage I lung adenocarcinoma patients, distinct genetic, genomic, epigenetic, and immunologic profiles of recurrent tumors were analyzed using a novel recurrence classifier. To characterize the tumor immune microenvironment of recurrent stage I tumors, unique tumor-infiltrating immune population markers were identified using single cell RNA-seq on a separate cohort of patients undergoing stage I lung adenocarcinoma resection and applied to a large study cohort using digital cytometry. Recurrent stage I lung adenocarcinomas demonstrated higher mutation and lower methylation burden than non-recurrent tumors, as well as widespread activation of known cancer and cell cycle pathways. Simultaneously, recurrent tumors displayed downregulation of immune response pathways including antigen presentation and Th1/Th2 activation. Recurrent tumors were depleted in adaptive immune populations, and depletion of adaptive immune populations and low cytolytic activity were prognostic of stage I recurrence. Genomic instability and impaired adaptive immune responses are key features of stage I lung adenocarcinoma immunosurveillance escape and recurrence after surgery.

SUBMITTER: Kratz JR

PROVIDER: S-EPMC8654957 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Genetic and immunologic features of recurrent stage I lung adenocarcinoma.

Kratz Johannes R JR Li Jack Z JZ Tsui Jessica J Lee Jen C JC Ding Vivianne W VW Rao Arjun A AA Mann Michael J MJ Chan Vincent V Combes Alexis J AJ Krummel Matthew F MF Jablons David M DM

Scientific reports 20211208 1

Although surgery for early-stage lung cancer offers the best chance of cure, recurrence still occurs between 30 and 50% of the time. Why patients frequently recur after complete resection of early-stage lung cancer remains unclear. Using a large cohort of stage I lung adenocarcinoma patients, distinct genetic, genomic, epigenetic, and immunologic profiles of recurrent tumors were analyzed using a novel recurrence classifier. To characterize the tumor immune microenvironment of recurrent stage I ...[more]

PMID: 34880292

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Genetic and immunologic features of recurrent stage I lung adenocarcinoma.

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Genetic and immunologic features of recurrent stage I lung adenocarcinoma.

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