The Tumor Microenvironment of High Grade Serous Ovarian Cancer PDF Download

Author: M. Sharon Stack
Publisher: MDPI
ISBN: 3038975540
Category : Biology (General)
Languages : en
Pages : 435

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This book is a printed edition of the Special Issue "The Tumor Microenvironment of High Grade Serous Ovarian Cancer" that was published in Cancers

Author: Kenneth P. Nephew
Publisher:
ISBN: 9783038975557
Category : Electronic books
Languages : en
Pages : 1

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Book Description
The Special Issue on high grade serous ovarian cancer (HGSOC) and the contribution of the tumor microenviroment (TME) consists of reviews contributed by leaders in the OC field. As HGSOC metastases have a highly complex TME, there is an urgent need to better understand the TME in general, its distinct components in particular, and the role of the TME in the context of disease recurrence and development of chemoresistance. The Special Issue incorporates the current understanding of the different parts of thd TME components, including the cancer cells themselves, the cells surrounding the cancer cells or stromal cells, and the cells of the immune system, which are attracted to the site of metastases. In addition to these cells of the TME, the role of various cellular factors made by the cells of the TME are also the subject of the reviews. In addition, reviews in this Special Issue cover the complex relationships between the molecular mechanisms of HGSOC progression, including genomic, epigenomic and transcriptomic changes and changes in the immune cell landscape, as these may provide attractive new molecular targets for HGSOC therapy.

Author: Juan Gilabert-Estellu00e9s
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Background: Lymphocytic infiltration areas (immunoreactive), frequently found in high-grade serous ovarian cancer (HGSOC), are associated with a better prognosis and increased survival. The cross-talk between tumour cells and lymphocytes conditions the capacity of the immune system (IS) to cope with the tumour in the so-called immune-checkpoints. Therefore, assessing IS-related genes and infiltration patters might provide valuable prognostic biomarkers. Methodology: This retrospective study includes 57 samples from patients with HGSOC who underwent cytoreductive surgery at Hospital General (Valencia). Clinical variables, the features of the lymphocytic infiltration (pattern, localization and degree) and the expression of immune-related genes (CD4, CD8, FOXP3, ICOSL, ICOS, PD-L2, TGFu03b21, CD25, IDO1, IL7R, PD-L1, CTL4, CXCR4, PD1, OX40, LGAL and CD137) were evaluated to assess prognosis. Results: The median age was 61.5 years, being the majority of patients in advanced FIGO stages (76.3% III-IV vs. 23.7%, I-II stages). Patients with u226565 years and III-IV stages showed a shorter overall survival (OS, 30.17 vs. 99.90 months, p=0.009; 38.73 months vs. NR, p=0.005, respectively). Regarding immunoreactive areas, patients with an intratumoural pattern of lymphocyte infiltration had better prognosis compared to those that only had a peritumoural pattern (OS: 44.57 months vs. NR, p=0.041). In addition, those with a diffuse infiltration pattern presented a better prognosis compared to those with a focal pattern (OS, 20.20 months vs. NR p=0.003). Regarding gene expression, 11 genes (CTLA4, FOXP3, CD25, CSCR4, IDO1, PD-1, PD-L1, PD-L2, OX40L, ICOS, ICOSL, LGAL9 and CD137 were found over-expressed, but only CD137 displayed a significant prognostic value (OS: 50 months vs NR, p=0.020). Conclusion: HGSOC represents a group of highly immunoreactive tumours. Best prognosis is represented by patients with an intratumoural and diffuse pattern of lymphocytic infiltration and lower CD137 expression, which may be considered as valuable prognostic markers. These interesting findings could open a new window for immunotherapeutic approaches in HGSOC.

Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309380499
Category : Medical
Languages : en
Pages : 397

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In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease-several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors. Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

Author: Julian Smazynski
Publisher:
ISBN:
Category :
Languages : en
Pages :

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High-grade serous ovarian cancer (HGSC) remains the most common and lethal subtype of ovarian cancer with a 5-year survival rate of ~30%, highlighting an urgent need for new treatments. Cancer immunotherapy has emerged as an efficacious strategy aimed at harnessing the exquisite capabilities of our immune system to destroy malignant cells. However, the development of more effective immunotherapies is hampered by our limited understanding of the phenotype of bona fide tumor-reactive T cells versus irrelevant bystanders. Further, T cells that exhibit tumor specificity appear to encompass a tissue resident memory (TRM) phenotype but combat a harsh immunosuppressive tumor microenvironment, often leading to an exhausted phenotypic state and evasion of immune-mediated destruction. These insights have led to rapid clinical implementation of so-called "checkpoint blockade" therapies that re-invigorate T cell-mediated tumor destruction by blocking surface inhibitory receptors or ligands. Thus, by identifying the phenotype of prognostically favourable TRM T cells and the immunosuppressive networks they face, my thesis work tackles a critical challenge in designing the next generation of therapeutic interventions for this disease. To address this challenge, I hypothesized that (1) the TRM phenotype could be modulated for improving adoptive T cell therapy; (2) TRM TIL characterized by the co-expression of CD103, PD-1, and CD39 in HGSC provide improved prognostic benefit indicative of enriched tumor reactivity; (3) the TIGIT/CD155 signalling axis plays a crucial role in shaping the immunosuppressive landscape impeding TRM T cells in HGSC. Firstly, I developed methods for modulating the TRM phenotype on expanded human and murine T cells for adoptive cell therapy and assessed the therapeutic impact of these phenotypes. Secondly, we applied high-dimensional flow cytometry, single-cell sequencing, and multiplexed immunofluorescence to primary human HGSC specimens to explore the single-cell phenotypic profiles and prognostic significance of tumor-infiltrating T cells co-expressing three putative markers of tumor reactivity: CD39, CD103, and PD-1. These 'triple-positive' T cells exhibited a highly activated/exhausted phenotype and superior prognostic value relative to all other T-cell subsets, suggesting these markers enrich for tumor-reactive clones. Furthermore, these triple-positive cells exhibited heightened expression of the inhibitory checkpoint TIGIT, which plays a prominent role in tumor-mediated immune suppression. Finally, to explore the therapeutic implications of this finding, we investigated the relationship between the TIGIT signaling axis on TIL and prognosis in HGSC. Once again utilizing high-dimensional flow cytometry, multi-color histological imaging, and gene expression profiling we found T cells from HGSC frequently express TIGIT ex vivo and post-clinical expansion. Further, CD155, the dominant ligand for TIGIT, was largely expressed on malignant epithelium in HGSC and showed a negative association with immune infiltration. Thus, TRM T cells represents a compelling immunotherapeutic immune subset in HGSC and one that could be bolstered by immune checkpoint inhibition of the TIGIT/CD155 axis.

Author: Viive Maarika Howell
Publisher: Frontiers Media SA
ISBN: 2889197697
Category : Medicine (General)
Languages : en
Pages : 178

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This eBook provides a compendium of the current state-of-the-art in research tools for, and understanding of, the critical research areas in epithelial ovarian cancer (EOC) with a strong emphasis on (HG-SOC). Research areas covered include therapy response and development, microenvironmental influences and the etiology and progression of EOC. Ten articles detail established and novel in vivo and in vitro model systems. These include primary and immortalized cell culture in 2D and 3D as well as genetically engineered, transgenic, spontaneous, syngeneic, classical xenograft and patient derived xenograft mouse models. The generation of genetically engineered mouse models of HG-SOC has been a major dilemma as models with the oncogenic aberrations common in the human malignancy do not accurately recapitulate HG-SOC. Conversely, commonly used HG-SOC cell lines have been found to not harbor the expected genetic changes. These issues as well as the rapid acceptance of patient derived xenograft models are reviewed. Five articles discuss different aspects of the tumor microenvironment including its role in therapy resistance, disease progression and metastasis. Mutation of BRCA1/2 continues to be the best defined risk factor for HG-SOC. Three articles discuss BRCA-loss in the context of disease development, targeted therapies and changes in preventative measures proposed for mutation carriers in light of the recent advances in knowledge regarding the origins of this malignancy. An image of HG-SOC with reduced BRCA1 expression is featured on the cover (image by VM Howell). A major clinical issue for patients with HG-SOC is the development of therapy resistance. Five articles focus on therapy resistance and different ways to overcome resistance. Overall, this eBook is an outstanding resource to aid researchers design their programs of research and determine the most appropriate and up-to-date EOC model systems to address their research questions.

Author: Leah Sommerfeld
Publisher:
ISBN:
Category :
Languages : de
Pages : 0

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Author: Goli Samimi
Publisher: Academic Press
ISBN: 0128198419
Category : Science
Languages : en
Pages : 190

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Overcoming Ovarian Cancer Chemoresistance presents non-overlapping review chapters that discuss the state of the field in overcoming chemoresistance of ovarian cancer and treatment options before and following recurrence, considering the genetic makeup of the ovarian cancer patient and her tumor. With the uptake of both germline and somatic gene testing, clinicians can obtain a more comprehensive understanding of ovarian tumors and this book provides information to link the genetic makeup of a tumor (or patient) with the best available treatment. The book discusses topics such as strategies to fight chemo-resistance in ovarian cancer, circulating DNA as a monitor of response, BRCA mutations, ovarian cancer stem cells, immunotherapy and vaccines. Additionally, it brings a list of promising agents at clinical and pre-clinical stage that will impact the treatment in the near future. This book is a valuable source for cancer researchers, oncologists and several members of biomedical field who need to understand how to battle chemoresistance in ovarian cancer. Provides a comprehensive view of both biological and genetic determinants of resistance, as well as technical approaches to monitor response Discusses genetic reversions as a unique alteration and a new field of study Includes a chapter on upcoming and promising agents that are in the pre-clinical and early clinical space, to set the stage for future directions in the field

Author: Eric Pujade-Lauraine
Publisher: Springer
ISBN: 3319321102
Category : Medical
Languages : en
Pages : 288

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This book provides an overview of the latest developments in the concepts and management of ovarian cancer. The new data presented throughout opens the way to radically different therapeutic approaches. Surgery remains the core of ovarian cancer treatment, but its ultimate goal and the standard surgical procedure have evolved, giving rise to the question of how to label expert centers for debulking surgery. Neo-adjuvant chemotherapy is becoming more popular and is also a new field for testing novel drug combinations. Over recent years, ovarian cancer management has embraced molecular biology. It is now more correct to talk about cancers of the ovary rather than ovarian cancer, since it is not a unique disease but several entities with different molecular drivers. The significant advances in drugs targeting the microenvironment or the tumor cell DNA repair mechanisms are presented in detail together with exciting future perspectives. All these advances would not have been possible without collaborative groups such as the GINECO group in France and their integration in wider clinical research networks at the European (ENGOT) and international (GCIG) level.

Author: Malcolm John Farquharson
Publisher:
ISBN:
Category : Ovaries
Languages : en
Pages : 0

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