Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer

Wang, Qinchaung; Gu, Jian; Wang, Linbo; Chang, David W.; Ye, Yuanqing; Huang, Maosheng; Roth, Jack A.; Wu, Xifeng

doi:10.1136/jitc-2019-000336

Cited by 10 publications

(8 citation statements)

References 32 publications

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“…Interestingly, in analyses stratified by stage, we found a greater number of significant associations between PRSs for cancers and immune traits than in overall association analyses. Previous studies have focused mainly on predicting prognosis according to the immune landscape in the early stages, owing to sample sizes [ 43 , 44 , 45 , 46 ]. Although this study had some sample size limitations, we systematically evaluated association analyses by early and advanced stages across the four cancer types.…”

Section: Discussionmentioning

confidence: 99%

Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers

Choi

Kim

Sung

et al. 2022

Cancers

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It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, we analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (p < 0.05) significance level, we identified 31 significant associations between PRS and immune traits. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.

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Section: Discussionmentioning

confidence: 99%

Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers

Choi

Kim

Sung

et al. 2022

Cancers

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“…PD-1/PD-L1 polymorphisms were associated with overall cancer susceptibility ( 47 ) and a prognostic impact ( 48 ). Although less studied, polymorphisms in IDO1 have been reported to be associated with overall survival in early stage cancer ( 49 , 50 ). In a cohort of healthy individuals, a polymorphism in the promoter region of IDO1 was associated with altered serum Trp concentrations ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma

et al. 2021

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Immune escape is an early phenomenon in cancer development/progression. Indoleamine 2,3-dioxygenase 1 (IDO1) is a normal endogenous mechanism of acquired peripheral immune tolerance and may therefore be tumor-promoting. This study investigated the clinical relevance of IDO1 expression by immune cells in the lymph nodes and blood and of the serum kynurenine/tryptophan (Kyn/Trp) ratio in 65 systemic treatment naïve stage I-III melanoma patients. Blood samples were collected within the first year of diagnosis. Patients had a median follow-up of 61 months. High basal IDO1 expression in peripheral monocytes and low IFNγ-induced IDO1 upregulation correlated with worse outcome independent from disease stage. Interestingly studied factors were not interrelated. During follow-up, the risk of relapse was 9% (2/22) in the subgroup with high IFNγ-induced IDO1 upregulation in monocytes. In contrast, if IDO1 upregulation was low, relapse occurred in 30% (3/10) of patients with low basal IDO1 expression in monocytes and in 61.5% (8/13) in the subgroup with high basal IDO1 expression in monocytes (Log-Rank test, p=0.008). This study reveals some immune features in the blood of early stage melanoma that may be of relevance for disease outcome. These may offer a target for sub-stratification and early intervention.

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“…A cohort study in south India reported that patients with the PDCD1LG2 SNP rs7854413 and lymphatic filariasis infection were susceptible to chronic lymphatic pathologies (40), and rs7854413 polymorphism was related to advanced fibrosis and development of hepatocellular carcinoma from patient with non-alcoholic steatohepatitis (41). Notably, rs7854413 was also associated with recurrence in patients with early-stage NSCLC (42). During the process of literature review, no studies on these PDCD1LG2 SNPs other than rs7854413 were reported.…”

Section: Discussionmentioning

confidence: 99%

Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

et al. 2021

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ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

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Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer

Cited by 10 publications

References 32 publications

Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers

Polygenic Risk Scores Associated with Tumor Immune Infiltration in Common Cancers

Clinical Relevance of Serum Kyn/Trp Ratio and Basal and IFNγ-Upregulated IDO1 Expression in Peripheral Monocytes in Early Stage Melanoma

Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

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