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Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

ABSTRACT: The purpose of this study is to compare transcriptional profiles of non-small-cell lung cancer between responder patients and non-responder patients during anti-PD-1 treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126043 | GEO | 2020/09/04

REPOSITORIES: GEO

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Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

Project description:The purpose of this study is to compare transcriptional profiles of non-small-cell lung cancer between responder patients and non-responder patients during anti-PD-1 treatment.

2020-02-03 | GSE126044 | GEO

Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer.

Project description:Although approved programmed cell death protein (PD)-1 inhibitors show durable responses, clinical benefits to these agents are only seen in one-third of patients in most cancer types. Therefore, strategies for improving the response to PD-1 inhibitor for treating various cancers including non-small cell lung cancer (NSCLC) are urgently needed. Compared with genome and transcriptome, tumor DNA methylome in anti-PD-1 response was relatively unexplored. We compared the pre-treatment methylation status of cis-regulatory elements between responders and non-responders to treatment with nivolumab or pembrolizumab using the Infinium Methylation EPIC Array, which can profile ~850,000 CpG sites, including ~350,000 CpG sites located in enhancer regions. Then, we analyzed differentially methylated regions overlapping promoters (pDMRs) or enhancers (eDMRs) between responders and non-responders to PD-1 inhibitors. We identified 1007 pDMRs and 607 eDMRs associated with the anti-PD-1 response. We also identified 1109 and 1173 target genes putatively regulated by these pDMRs and eDMRs, respectively. We found that eDMRs contribute to the epigenetic regulation of the anti-PD-1 response more than pDMRs. Hypomethylated pDMRs of Cytohesin 1 Interacting Protein (CYTIP) and TNF superfamily member 8 (TNFSF8) were more predictive than programmed cell death protein ligand 1 (PD-L1) expression for anti-PD-1 response and progression-free survival (PFS) and overall survival (OS) in a validation cohort, suggesting their potential as predictive biomarkers for anti-PD-1 immunotherapy. The catalog of promoters and enhancers differentially methylated between responders and non-responders to PD-1 inhibitors presented herein will guide the development of biomarkers and therapeutic strategies for improving anti-PD-1 immunotherapy in NSCLC.

| S-EPMC8080767 | biostudies-literature

Proteomics of the Gastric cancer Response to anti-PD1 therapy

Project description:To validate the correlation between Th1/Th2 ratio and immunotherapeutic effectiveness, we collected a group of GC patients treated with anti-PD1 therapy, including 7 responder cases (PR) and 7 non-responder cases (SD/PD). The formalin-fixed paraffin-embedded (FFPE) tumor tissue sections derived from 14 therapy-naïve GC patients were collected.

2022-11-17 | PXD038188 |

Identification of differentially expressed miRNAs in PD vs. nonPD in cancer samples

Project description:Lack of a standard method for stratifying advanced-stage NSCLC patients receiving platinum combination therapy often results in a number of patients that do not derive benefit yet are still exposed to treatment toxicity. We hypothesized that miRNAs in pre-treatment serum and/or plasma could be used to differentiate non-small cell lung cancer (NSCLC) patients who would have disease progression to first-line carboplatin and gemcitabine chemotherapy at first response assessment. miRNA profiling of mature and precursor miRNAs was performed on total RNA isolated from the pre-treatment serum and plasma of 24 NSCLC patients. Single validated candidates or combinations thereof were selected based on specificity and sensitivity to segregate patients with disease progression at first radiologic response (PD) vs. those without progressed disease (nonPD). Two precursor miRNA were significantly over-expressed in serum (but not plasma) of PD patients: pre-miR-518b and pre-miR-598. Serum miRNAs may serve as a screening tool in predicting chemoresistance to platinum-based combination chemotherapy. miRNA microarray was performed on RNA extracted from matched human serum or plasma obtained from NSCLC patients

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Proteomic profiling to predict therapeutic response to anti-PD1 therapy in advanced melanoma

Project description:Purpose Antibody-blockade of PD-1 shows durable responses, but so far, few biomarkers accurately predict if patients with metastatic melanoma will respond. Experimental design We analyzed baseline serum samples (n=56) and tumor cell cultures (n=8), from melanoma patients treated with anti-PD1 therapy. Two approaches concentrating low abundant proteins in serum and two different mass spectrometry (MS) methods were applied: depletion of high abundant proteins with shotgun-MS, and N-glycosite enrichment combined with SWATH-MS. Tumor cell cultures were processed as whole cell lysates with subsequent shotgun-MS. Results Focusing on the non-responder proteome, we identified pathways such as inflammatory processes, cell adhesion and migration, scavenger receptor activity, RAGE receptor binding, platelet aggregation, neutrophil degranulation and integrin signaling to be upregulated. Analyzing the tumor cell proteome revealed a distinctive immunophenotype with CD antigens highly overexpressed in non-responders. Validation of a subset of these markers, performed by immunofluorescence staining of a tissue microarray, revealed a higher mean of positive cells in the tumor microenvironment of non-responders. Validation of serum proteome markers on a second baseline cohort by using a timsTOF for ion mobility MS, revealed significant differences between responder and non-responder for the proteins ORM2, SERPINA1, EFEMP1, and VASN. TCGA survival analysis demonstrated prognostic significance for multiple proteins of our signature correlating with lower overall survival in melanoma patients. Based on this study, we suggest a protein-panel for responsiveness to PD-1 blockade consisting of 14 serum and 33 tumor cell markers that will be the basis for further research.

2023-08-18 | PXD027525 | Pride

Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

Project description:Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

| PRJNA520852 | ENA

Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

Project description:Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

| PRJNA520851 | ENA

Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

Project description:Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

| PRJNA520848 | ENA

Genome-wide identification of differentially methylated promoters and enhancers associated with response to anti-PD-1 therapy in non-small cell lung cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-02-03 | GSE126045 | GEO

Single cell sequencing of anti-PD-1 treated xenograft from mice bladder urothelium with Trp53, Rb1, PTEN mutations on C57 BL/6J

Project description:To determine the immune mechanism of anti-PD1 therapy, we carried out an anti-PD1 treatment on C57 BL/6J mice bearing mouse bladder urothelial carcinoma with three gene knockout. Anti-PD-1 immunotherapy resulted in a mixed pattern of treatment responses in individual tumors. Then, we performed single cell transcriptome profiling for tumor xenografts from Control IgG, anti-PD-1 non-responders and anti-PD-1 responders group. Duplicate tumors in each group were mixed and sequenced together as one representative sample. In results, we captured 4762 cells from Control IgG group, 4459 cells from anti-PD-1 non-responders group and 4861 cells from anti-PD-1 responders group. identified 8 clusters of immune cells in treated samples (basophils, B cells, dendritic cells, macrophages, monocytes, neutrophils, NK cells, and T cells). Responder xenografts displayed significantly increased immune cell infiltration (15.2%, 742 immune cells / 4861 total cells) compared to the non-responder tumors (10.1%, 452 immune cells/ 4459 total cells, Fisher Exact Test p<0.0001). Specifically, there were more T cells (46/4861 vs 18 /4459, p=0.002), and macrophages (420/4861 vs 287/4459, p=0.002) in responder xenografts than in non-responder xenografts. Compared to control IgG tumors, response tumors exhibited an immune-inflamed phenotype with significant infiltration of T cells and NKT cells, whereas non-responder tumors showed no significant change. The higher percentage of T cells and macrophages tumor infiltration in responders suggests a potential role of innate immune microenvironment for the Immune checkpoint inhibitor (ICI) treatment response. This study provides the insights of immune environments in ICI-treated bladder tumor xenograft on C57 mice.

2022-06-01 | GSE200139 | GEO

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