Type of chemotherapy has substantial effects on the immune system in ovarian cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Vankerckhoven A
PROVIDER: S-EPMC8022256 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Histopathological and molecular studies suggest that different histological subtypes (histotypes) of ovarian cancer have different aetiologies. Few studies have been large enough to explore reliably the effect of tubal ligation (sterilization), which has been associated with a reduced overall risk of ovarian cancer, on different tumour histotypes. In a prospective study of 1.1 million UK women without prior cancer or bilateral oophorectomy, 8,035 ovarian cancers occurred during mean follow-up of 13.8 years. Using a Cox proportional hazards model, we estimated adjusted relative risks of ovarian cancer associated with tubal ligation. Overall, there was substantial heterogeneity in tumour risk associated with tubal ligation for the four main histotypes, serous, endometrioid, mucinous and clear cell (heterogeneity: p < 0.0001). For serous tumours, the most common histotype (n = 3,515), risks differed significantly between high-grade (RR: 0.77, 95% CI: 0.67-0.89) and low-grade tumours (RR: 1.13, 95% CI: 0.89-1.42); heterogeneity: p = 0.007. Relative risks were almost halved for endometrioid (n = 690, RR: 0.54, 95% CI: 0.43-0.69) and clear cell tumours (n = 401, RR: 0.55, 95% CI: 0.39-0.77), but there was no association between tubal ligation and mucinous tumours (n = 836, RR: 0.99, 95% CI: 0.84-1.18). For the main tumour histotypes we found little variation of risk by timing of tubal ligation. The significant differences by tumour histotype are unlikely to be due to confounding and are consistent with hypotheses that high-grade and low-grade serous tumours have different origins, and that some endometrioid and clear cell tumours might arise from cells and/or carcinogens travelling through the fallopian tubes.
| S-EPMC4832307 | biostudies-other
Project description:Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks.
| S-EPMC3940260 | biostudies-literature
Project description:Neoadjuvant chemotherapy (NACT) may stimulate anticancer adaptive immune responses in high-grade serous ovarian cancer (HGSOC), but little is known about effects on innate immunity. Using omental biopsies from HGSOC, and omental tumors from orthotopic mouse HGSOC models that replicate the human tumor microenvironment, we studied the impact of platinum-based NACT on tumor-associated macrophages (TAM). We found that chemotherapy reduces markers associated with alternative macrophage activation while increasing expression of proinflammatory pathways, with evidence of inflammasome activation. Further evidence of a shift in TAM functions came from macrophage depletion via CSF1R inhibitors (CSF1Ri) in the mouse models. Although macrophage depletion in established disease had no impact on tumor weight or survival, CSF1Ri treatment after chemotherapy significantly decreased disease-free and overall survival. This decrease in survival was accompanied by significant inhibition of adaptive immune response pathways in the tumors. We conclude that chemotherapy skews the TAM population in HSGOC toward an antitumor phenotype that may aid adaptive immune responses, and therapies that enhance or sustain this during remission may delay relapse.
| S-EPMC7611478 | biostudies-literature
Project description:In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME 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 NACT, increased natural killer (NK) 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.
| S-EPMC8353209 | biostudies-literature
Project description:BackgroundEpithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer.ObjectivesTo assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL).Search methodsIn the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, The Cochrane Central Register of Controlled Trails (CENTRAL, The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For this update, the searches were extended to October 2012.Selection criteriaRandomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy.Data collection and analysisTwo review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression-free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention-to-treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs.Main resultsWe included eight trials (1644 women). When all chemotherapy regimens were combined, meta-analysis indicated no significant difference in three-, five- and 10-year OS or PFS. For five-year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10) and for the five-year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10-year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three- and five-year OS rates have no significant difference between the two groups.Authors' conclusionsThere is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required.
| S-EPMC6457821 | biostudies-literature
Project description:BackgroundOvarian cancer (OC) is one of the most lethal gynecological malignancies. This study aimed to identify biomarkers that were sensitive to platinum-based chemotherapeutic agents and can be used in immunotherapy and explore the importance of their mechanisms of action.MethodsRNA-seq profiles and clinicopathological data for OC samples were obtained from The Cancer Genome Atlas (TCGA) and cBioPortal platform, respectively. Platinum-sensitive and platinum-resistant OC samples in the TCGA cohort were selected based on the clinical information. RNA-seq data for 70 OC samples withSingle-sample gene set enrichment analysis (ssGSEA) and unsupervised clustering were used to classify OC patients from the TCGA cohort into clusters with different proportions of infiltrating immune cells. ESTIMATE analysis was used to assess the immune landscape among clusters. Differential expression, univariate Cox regression, and LASSO regression analyses were performed to construct prognostic model. Spearman correlation analysis was conducted to investigate the correlations among immune checkpoint inhibitors (ICIs) and risk score, half-maximal drug inhibitory concentration (IC50) and risk score.ResultsUsing ssGSEA and unsupervised clustering, OC samples were divided into two clusters with different immune cell infiltration. Then, 1715 differentially expressed immune-related genes (DEIRGs) were identified between two clusters, 984 differentially expressed platinum-sensitive related genes (DEPSRGs) between 149 platinum-sensitive and 63 platinum-resistant OC samples were identified, and 5384 differentially expressed genes (DEGs) between 380 OC and 194 normal samples were detected from the TCGA cohort. Six biomarkers (GMPPB, SRPK1, STC1, PRSS16, HPDL, and SPTSSB) were detected to establish a prognostic model. The OC patients in the TCGA cohort were classified into high- and low-risk groups. The receive operating characteristic (ROC) curve was plotted and demonstrated that the prognostic model performed well with the area under ROC curve (AUC) greater than 0.6. The expressions of 5 ICIs, including CD200, TNFRSF18, CD160, CD200R1, and CD274 (PD-L1), were significantly different between two risk groups, and the risk score was significant negative associated with CTLA4, TNFRSF4, TNFRSF18, and CD274. Moreover, there were significant differences in IC50 of 10 chemo drugs between two risk groups, patients in the high-risk group could be more resistant to po0tinib, dasatinib, and neratinib.ConclusionIn summary, this study constructed a novel prognostic model based on six prognostic biomarkers, including GMPPB, SRPK1, STC1, PRSS16, HPDL, and SPTSSB, which can be utilized for predicting the prognosis of OC patients. These biomarkers were the potential therapeutic targets.
| S-EPMC10458992 | biostudies-literature
Project description:BackgroundOvarian cancer is the leading cause of cancer-related death among women. Complete cytoreductive surgery followed by platinum-taxene chemotherapy has been the gold standard for a long time. Various compounds have been assessed in an attempt to combine them with conventional chemotherapy to improve survival rates or even overcome chemoresistance. Many studies have shown that an antidiabetic drug, metformin, has cytotoxic activity in different cancer models. However, the synergism of metformin as a neoadjuvant formula plus chemotherapy in clinical trials and basic studies remains unclear for ovarian cancer.MethodsWe applied two clinical databases to survey metformin use and ovarian cancer survival rate. The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy.ResultsWe found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin. The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. In combination with chemotherapy, the neoadjuvant metformin protocol showed beneficial synergistic effects in vitro and in vivo.ConclusionsThis study shows that neoadjuvant metformin at clinically relevant dosages is efficacious in treating ovarian cancer, and the results can be used to guide clinical trials.
| S-EPMC7442990 | biostudies-literature
Project description:The sphingolipid and lysophosphatidate regulatory networks impact diverse mechanisms attributed to cancer cells and the tumor immune microenvironment. Deciphering the complexity demands implementation of a holistic approach combined with higher-resolution techniques. We implemented a multi-modular integrative approach consolidating the latest accomplishments in gene expression profiling, prognostic/predictive modeling, next generation digital pathology, and systems biology for epithelial ovarian cancer. We assessed patient-specific transcriptional profiles using the sphingolipid/lysophosphatidate/immune-associated signature. This revealed novel sphingolipid/lysophosphatidate-immune gene-gene associations and distinguished tumor subtypes with immune high/low context. These were characterized by robust differences in sphingolipid-/lysophosphatidate-related checkpoints and the drug response. The analysis also nominates novel survival models for stratification of patients with CD68, LPAR3, SMPD1, PPAP2B, and SMPD2 emerging as the most prognostically important genes. Alignment of proprietary data with curated transcriptomic data from public databases across a variety of malignancies (over 600 categories; over 21,000 arrays) showed specificity for ovarian carcinoma. Our systems approach identified novel sphingolipid-lysophosphatidate-immune checkpoints and networks underlying tumor immune heterogeneity and disease outcomes. This holds great promise for delivering novel stratifying and targeting strategies.
| S-EPMC6479272 | biostudies-literature
Project description:We explore the potential of immune-associated expression profiles in a series of Epithelial Ovarian Cancer (EOC) patients undergoing neoadjuvant chemotherapy (NACT), comparing primary lesions before patients underwent carboplatin/paclitaxel-based NACT (so-called ´biopsy samples´) and interval debulking surgery (IDS) samples from residual lesions after treatment with chemotherapy (so-called ´surgery samples´).
2022-01-27 | GSE181597 | GEO
Project description:Simple Summary Neoadjuvant chemotherapy (NAC) induced a dynamic change in the TIME that increased the level of immune infiltration, leading to a high number of CD8 T cells with enhanced immune activity. However, increased immune infiltration and immune activity did not present any survival benefit, probably due to concomitant immunosuppression associated with an increase in the proportion of Foxp3+ regulatory T cells. Our results could provide therapeutic strategies to improve the survival benefit from immunotherapies in an NAC setting. Abstract The dynamic changes in the tumor immune microenvironment (TIME) triggered by neoadjuvant chemotherapy (NAC) have not been clearly defined in advanced-stage ovarian cancer. We analyzed the immunologic changes induced by NAC to correlate them with clinical outcomes. We compared the changes in the immune infiltration of high-grade serous carcinoma biopsies before and after NAC via immunohistochemistry (147 paired samples) and whole transcriptome sequencing (35 paired samples). Immunohistochemistry showed significantly increased PD-L1 levels and TIL levels after NAC. Whole transcriptome sequencing revealed that the stromal score, immune score, and cytolytic activity score significantly increased after NAC. An increased tumor-infiltrating lymphocyte (TIL) level in response to NAC was associated with shorter progression-free survival compared with decreased TIL level after NAC. In tumors with increased TIL levels after NAC, the relative fraction of CD8 T cells and regulatory T cells significantly increased with immunohistochemistry. Post-NAC tumors were enriched in gene sets associated with immune signaling pathways, such as regulatory T cell and JAK/STAT signaling pathways. NAC induced dynamic changes in the TIME that increased TIL levels, but their high abundance did not impart any survival benefit. Our data may provide therapeutic strategies to improve the survival benefit from immunotherapies in ovarian cancer.
| S-EPMC9104540 | biostudies-literature