Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227100 | GEO | 2023/06/21
REPOSITORIES: GEO
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Project description:IntroductionOvarian cancer recurs in most High Grade Serous Ovarian Cancer (HGSOC) patients, including initial responders, after standard of care. To improve patient survival, we need to identify and understand the factors contributing to early or late recurrence and therapeutically target these mechanisms. We hypothesized that in HGSOC, the response to chemotherapy is associated with a specific gene expression signature determined by the tumor microenvironment. In this study, we sought to determine the differences in gene expression and the tumor immune microenvironment between patients who show early recurrence (within 6 months) compared to those who show late recurrence following chemotherapy.MethodsPaired tumor samples were obtained before and after Carboplatin and Taxol chemotherapy from 24 patients with HGSOC. Bioinformatic transcriptomic analysis was performed on the tumor samples to determine the gene expression signature associated with differences in recurrence pattern. Gene Ontology and Pathway analysis was performed using AdvaitaBio's iPathwayGuide software. Tumor immune cell fractions were imputed using CIBERSORTx. Results were compared between late recurrence and early recurrence patients, and between paired pre-chemotherapy and post-chemotherapy samples.ResultsThere was no statistically significant difference between early recurrence or late recurrence ovarian tumors pre-chemotherapy. However, chemotherapy induced significant immunological changes in tumors from late recurrence patients but had no impact on tumors from early recurrence patients. The key immunological change induced by chemotherapy in late recurrence patients was the reversal of pro-tumor immune signature.DiscussionWe report for the first time, the association between immunological modifications in response to chemotherapy and the time of recurrence. Our findings provide novel opportunities to ultimately improve ovarian cancer patient survival.
| S-EPMC10331425 | biostudies-literature
Project description:Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer
| PRJNA943229 | ENA
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
Project description:In metastatic cancer, the degree of heterogeneity of the tumor-immune microenvironment and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy in high-grade serous ovarian cancer (HGSOC), we performed immunogenomics analysis of treatment-naive and paired pre/post-chemotherapy treated samples. In treatment-naive HGSOC, we find that immune cell-excluded and inflammatory microenvironments co-exist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of tumor microenvironment cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following neoadjuvant chemotherapy, increased natural killer cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors. The goal of this particular experiment was quantify RNA expression using microarray technology, and then evaluate differences in the trasncirptomic landscape of treatment naïve metastatic high grade serous ovarian cancer.
2020-03-14 | GSE146964 | GEO
Project description:Most high-grade serous ovarian cancer (HGSOC) patients develop resistance to platinum-based chemotherapy and recur, but 15% remain disease-free over a decade. To discover drivers of long-term survival, we quantitatively analyzed the proteomes of platinum resistant and sensitive HGSOC patients from minute amounts of formalin-fixed, paraffin-embedded tumors. This revealed cancer/testis antigen 45 (CT45) as an independent prognostic factor associated with a doubling of disease-free survival in advanced stage HGSOC. Phospho- and interaction proteomics tied CT45 to DNA damage pathways through direct interaction with the PP4 phosphatase complex. In vitro, CT45 regulated PP4 activity and its high expression led to increased DNA damage and platinum sensitivity. CT45-derived HLA class I peptides, identified by immunopeptidomics, activate patient-derived cytotoxic T cells and promote tumor cell killing. This study highlights the power of clinical cancer proteomics to identify targets for chemo- and immunotherapy and illuminate their biological roles.
2020-04-19 | PXD010372 | Pride
Project description:In metastatic cancer, the degree of heterogeneity of the tumor-immune microenvironment and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy in high-grade serous ovarian cancer (HGSOC), we performed immunogenomics analysis of treatment-naive and paired pre/post-chemotherapy treated samples. In treatment-naive HGSOC, we find that immune cell-excluded and inflammatory microenvironments co-exist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of tumor microenvironment cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following neoadjuvant chemotherapy, increased natural killer cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors. The goal of this particular experiment was quantify RNA expression using microarray technology, and then evaluate differences in the trasncirptomic landscape of treatment naïve metastatic high grade serous ovarian cancer.
2020-03-14 | GSE146963 | GEO
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. 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.
2016-07-27 | E-GEOD-71340 | biostudies-arrayexpress
Project description:The impact of platinum and taxol based neoadjuvant chemotherapy on tumour-associated macrophages (TAMs) was examined by analysis of TAMs extracted from high grade serous ovarian cancer (HGSOC) samples pre and post chemotherapy.
2021-04-20 | GSE158739 | GEO
Project description:High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve the cure rate of HGSOC. Liquid biopsies are now becoming a new paradigm to develop novel biomarkers with diagnostic and prognostic purposes. The focus of this study was to detect the levels of circulating miRNAs in tissues and sera from patients with HGSOC and to evaluate their diagnostic value. To this end, an array-based discovery platform, followed by an innovative statistical approach of data normalization, was exploited, to identify miRNA species selectively expressed in serum of patients with HGSOC. Sera from 106 high grade serous ovarian carcinoma (HGSOC) and 24 healthy controls were used for profiling serum microRNA using a modified version of a commercially available microarray, with the aim of identifying differentially expressed microRNA between tumor patients and healthy controls.
2017-01-30 | E-MTAB-4667 | biostudies-arrayexpress
Project description:High-grade serous ovarian cancer (HGSOC) is responsible for the largest number of ovarian cancer deaths. The frequent therapy-resistant relapses necessitate a better understanding of mechanisms driving therapy-resistance. Therefore, we mapped more than hundred thousand cells of HGSOC patients in different phases of the disease, using single-cell RNA sequencing. Within patients, we compared chemonaive with chemotreated samples. As such, we were able to create a single cell atlas of different HGSOCs lesions and their treatment.
2022-07-06 | GSE201047 | GEO