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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Neoadjuvant chemotherapy modulates T cell responses in high-grade serous ovarian cancer metastases

ABSTRACT: Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy. tRNA was isolated from 35 omental tissue samples of HGSOC metastases either pre or post NACT treatment. RNASeq was performed on poly-A selected mRNA fragments, 100 b.p paired end, and strand specific, on average 40 million reads per sample.

ORGANISM(S): Homo sapiens

SUBMITTER: Oliver Pearce

PROVIDER: E-GEOD-71340 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma.

Böhm Steffen S Montfort Anne A Pearce Oliver M T OM Topping Joanne J Chakravarty Probir P Everitt Gemma L A GL Clear Andrew A McDermott Jackie R JR Ennis Darren D Dowe Thomas T Fitzpatrick Amanda A Brockbank Elly C EC Lawrence Alexandra C AC Jeyarajah Arjun A Faruqi Asma Z AZ McNeish Iain A IA Singh Naveena N Lockley Michelle M Balkwill Frances R FR

Clinical cancer research : an official journal of the American Association for Cancer Research 20160601 12

<h4>Purpose</h4>The purpose of this study was to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSC), and its relationship to treatment response.<h4>Experimental design</h4>We obtained pre- and posttreatment omental biopsies and blood samples from a total of 54 patients undergoing platinum-based NACT and 6 patients undergoing primary debulking surgery. We measured T-cell density and phenotype, immune activatio ...[more]

PMID: 27306793

Similar Datasets

Molecular Response to Neoadjuvant Chemotherapy in High-Grade Serous Ovarian Carcinoma

Project description:While high-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype of ovarian cancer, significant tumor heterogeneity exists. In addition, chemotherapy induces changes in gene expression and alters the mutational profile. To evaluate the notion that patients with HGSOC could be better classified for optimal treatment based on gene expression, we compared genetic variants (by DNA next-generation sequencing [NGS] using a 50 gene Ion Torrent panel) and gene expression (using the NanoString® PanCancer 770 gene Panel) in the tumor from 20 patients with HGSOC before and after neoadjuvant chemotherapy (NACT). NGS was performed on plasma cell free DNA (cfDNA) on a select group of patients (n=14) in order to assess the utility of using cfDNA to monitor these changes. A total of 86 genes had significant changes in RNA expression after NACT. Thirty-eight genetic variants (including SNPs) from 6 genes were identified in tumors pre-NACT, while 59 variants from 19 genes were detected in the cfDNA. The number of DNA variants were similar after NACT. Of the 59 variants in the plasma pre-NACT, only 6 persisted; whereas 33 of 38 specific variants in the tumor DNA remained unchanged. Pathway analysis showed the most significant alterations in the cell cycle and DNA damage pathways.

2018-02-01 | GSE109934 | GEO

Proteomic Alterations Associated with Residual Disease in Neoadjuvant Chemotherapy Treated Ovarian Cancer Tissues

Project description:Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome in the management of high-grade serous ovarian cancer (HGSOC) patients. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) offers an alternate approach to management of HGSOC patients to achieve complete resection. This study assessed proteomic alterations in matched, chemotherapy naïve and NACT-treated patients tumors obtained from HGSOC patients with suboptimal (R1) versus optimal (R0) debulking at IDS. We describe distinct proteome profiles in pre- and post-NACT HGSOC tumors correlating with residual disease status providing prognostic biomarkers for residual disease at IDS as well as candidate proteins associated with NACT resistance warranting further pre-clinical investigation.

2022-10-05 | PXD031929 | Pride

Genome wide co-localization of Polycomb orthologs and their effects on gene expression in human fibroblasts

Project description:We have identfied antibodies that support chromatin immunoprecipitation (ChIP) of 11 components of Polycomb repressive complex 1 (PRC1) and shown that multiple variants of PRC1 associate with the same DNA. By performing ChIP-seq with antibodies against CBX6, CBX7, CBX8, RING1 and RING2, in two strains of human fibroblasts, we find that all five proteins co-localize at multiple sites in the genome. The binding profiles have inherent architecture that is conserved between the two strains, but there are also a substantial number of differences between the strains, possibly reflecting their anatomical position. The presence of PcG proteins does not equate with gene silencing and their genomic position does not change at senescence. Chromatin immunoprecipitation and sequencing (ChIP-seq) in two strains of human fibroblasts using antibodies against three Pc orthologs (CBX6, CBX7 and CBX8) and both Psc orthologs (RING1 and 2). Validation by ChIP-PCR and re-ChIP. Strand specific RNA-seq and validation by qRT-PCR.

2013-12-19 | E-GEOD-40740 | biostudies-arrayexpress

Neoadjuvant chemotherapy modulates T cell responses in high-grade serous ovarian cancer metastases

Project description:Our data suggest that neoadjuvant chemotherapy enhances anti-cancer responses of T cells in peritoneal metastases of patients with high-grade serous ovarian cancer but does not decrease levels of immune checkpoint molecules, providing a rationale for sequential chemo-immunotherapy.

2016-07-27 | GSE71340 | GEO

RNA-Seq of pre-chemo high-grade serous ovarian tumors

Project description:We performed RNA sequencing on 10 bulk pre-chemo tumor samples collected from 5 patients with HGSOC.

2020-12-14 | GSE160085 | GEO

NanoString expression profiling in metastatic ovarian cancer

Project description:Purpose: Most molecular characterizations of high-grade serous ovarian cancer (HGSOC) have been done in primary ovarian tumors. Such data may not be fully representative of HGSOC, which is characterized by widespread peritoneal metastases at the time of diagnosis and upon relapse. The most common site of HGSOC metastasis is the omentum. The omentum is characterized by strong immune and fibrotic activities and is a rich source of mesenchymal stem cells (MSCs), which have the capacity to differentiate into cancer-associated fibroblasts (CAFs) and promote ovarian cancer progression. The omentum is also rich in tertiary lymphoid structures (TLS), which are transient aggregates of leukocytes structurally and functionally comparable to secondary lymphoid tissues. Experimental design: With the goal of elucidating expression patterns in a large number of omental metastases, we profiled expression of immune- and cancer progression-related genes in pretreatment omental metastasis samples from 152 patients diagnosed with HGSOC.

2020-07-02 | GSE135712 | GEO

Genome-wide expression profiling of mediastinal lymph nodal metastasis of stage IIIA NSCLC patients before neoadjuvant chemotherapy

Project description:Non–small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide due to late diagnosis and lack of effective therapies to treat metastatic disease. About one third of NSCLC patients present at diagnosis with locally advanced cancer (stage IIIA) which metastasizes ipsilateral mediastinal or subcarinal lymph nodes (N2). Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for resectable N2 disease. However, the majority of patients do not respond to NACT and show persistent lymph nodal metastases and an adverse outcome. Our scant knowledge of the molecular biology of lymph node metastases (LNmets) represents a major obstacle to develop more effective therapies. Here, we investigated gene expression profile (coding and non-coding) of LNmets collected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy, in two cohorts of stage IIIA patients before NACT (N=70). We discovered a microRNA expression signature in LNmets predictive of NACT response of N2 patients. Importantly, we unveiled a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance and impact T cell viability in NSCLC. Our data suggests the relevance of LNmets molecular profiling to predict response to NACT likewise presents strong evidences of a miRNA-based mechanism which functionally links chemotherapy response with PD-L1 regulation.

2022-12-31 | GSE193707 | GEO

Neoadjuvant and adjuvant pembrolizumab for advanced high-grade serous carcinoma (NeoPembrOV): A randomized phase II GINECO clinical trial

Project description:PD-1/PD-L1 blockade did not show survival benefit in high grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial and by combining RNA-seq and multiplexed immunofluorescence stainings, we explored the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment and identified parameters correlating to response. 1) The combination therapy resulted in a significant increase of intraepithelial CD8+PD-1+ T cells that correlated to clinical benefit. 2) High CD8B/FOXP3 and high CD8B/ENTPD1 ratios were significantly associated with response to NACT+P, while KDR and VEGFR2 expression were associated with resistance. 3) Combining endothelial and monocyte signatures and the CD8B/FOXP3 ratio predicted response to NACT+P with an AUC of 0.93 (95% CI 0.84–1.00). These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome ovarian cancer immune resistance.

2024-02-26 | GSE227666 | GEO

The impact of neoadjuvant chemotherapy on tumor microenvironment in advanced high-grade serous carcinoma

Project description:High-grade serous ovarian, fallopian tube or peritoneal carcinoma is an aggressive subtype that frequently develops resistance to chemotherapy. It remains controversial whether the resistance is caused by the acquisition of new molecular aberrations or alternatively through the selection of rare preexisting tumor clones. To address this question, we applied single cell RNA sequencing to depict the tumor landscape of a single case of advanced high-grade serous fallopian tube carcinoma during neoadjuvant chemotherapy (NACT).

2022-08-16 | GSE191301 | GEO

Immunologic adapatations of high grade serous ovarian cancer patients to neoadjuvant carboplatin and paclitaxel therapy

Project description:770 genes as well as pathways and deconvoluted immune cell types were determined pre- and post-neoadjuvant chemotherapy in a cohort of 31 stage III-IV high grade serous ovarian cancer (HGSOC) patients, and associations were made with the duration of their platinum-free interval n/a

2022-09-28 | GSE201600 | GEO

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