Dataset Information

Earlier-Phased Cancer Immunity Cycle Strongly Influences Cancer Immunity in Operable Never-Smoker Lung Adenocarcinoma.

ABSTRACT: Exome and transcriptome analyses of clinically homogeneous early-stage never-smoker female patients with lung adenocarcinoma were performed to understand tumor-T cell interactions and immune escape points. Using our novel gene panels of eight functional categories in the cancer-immunity cycle, three distinct subgroups were identified in this immune checkpoint blockade-refractory cohort by defective gene expression in two major domains, i.e., type I interferon production/signaling pathway and antigen-presenting machinery. Our approach could play a critical role in understanding immune evasion mechanisms, developing a method for effective selection of rare immune checkpoint blockade responders, and finding new treatment strategies.

SUBMITTER: Kim HK

PROVIDER: S-EPMC7426575 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Earlier-Phased Cancer Immunity Cycle Strongly Influences Cancer Immunity in Operable Never-Smoker Lung Adenocarcinoma.

Kim Hong Kwan HK Joung Je-Gun JG Choi Yoon-La YL Lee Se-Hoon SH Park Byung Jo BJ Choi Yong Soo YS Ryu Daeun D Nam Jae-Yong JY Lee Mi-Sook MS Park Woong-Yang WY Hwang Soohyun S Cha Hongui H Kim Hong Sook HS Lee Sanghyuk S Jung Yeonjoo Y Lee Jong Eun JE Doh Junsang J Paik Soonmyung S Kang Jung Hee JH Lee Jinseon J Kim Jhingook J

iScience 20200718 8

Exome and transcriptome analyses of clinically homogeneous early-stage never-smoker female patients with lung adenocarcinoma were performed to understand tumor-T cell interactions and immune escape points. Using our novel gene panels of eight functional categories in the cancer-immunity cycle, three distinct subgroups were identified in this immune checkpoint blockade-refractory cohort by defective gene expression in two major domains, i.e., type I interferon production/signaling pathway and ant ...[more]

PMID: 32795913

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Project description:Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment. To better understand the potential contribution of DNA methylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed a comprehensive, genome-wide profiling of DNA methylation in 17 primary non-small cell lung cancer and 10 matched normal lung samples using the complementary methylation assays MeDIP-seq and MRE-seq. Compared to patient-matched non-malignant lung tissue, we report recurrent methylation changes of several gene promoters, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), and PCDH7, NKX2-1, and SOX17 (hypermethylation). Although smoker and never-smoker patients shared many methylation changes, several were specific and recurrent within a particular smoking status. In particular, never-smokers displayed a greater proportion of hypoDMRs and exhibited a greater number of recurrently hypomethylated promoters, including the promoter of the oncogene ASPSCR1, and others previously linked to cancer, including TOP2A, DPP9, and USP39. Methylation changes outside of promoters were also widespread and often recurrent, particularly the loss of methylation over repetitive elements, highly enriched for ERV1 subfamilies. Recurrent hypoDMRs were also enriched for several transcription factor (TF) binding motifs, often for genes involved in signaling and cell proliferation, including 71% encoding a binding site of NKX2-1, which was found to be significantly upregulated in TCGA LUAD samples. Furthermore, the overwhelming majority of DMRs identified in this study were found to reside in an active chromatin state in at least one tissue profiled using the Roadmap Epigenome data, suggesting that methylation changes may contribute to altered regulatory programs through the adaptation of cell type-specific expression programs.

Dataset Information

Earlier-Phased Cancer Immunity Cycle Strongly Influences Cancer Immunity in Operable Never-Smoker Lung Adenocarcinoma.

Publications

Earlier-Phased Cancer Immunity Cycle Strongly Influences Cancer Immunity in Operable Never-Smoker Lung Adenocarcinoma.

Similar Datasets

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