Ascites modulates cancer cell behavior, contributing to tumor heterogeneity in ovarian cancer

Kim, Soochi; Kim, Boyun; Song, Yong Sang

doi:10.1111/cas.12987

Cited by 144 publications

(161 citation statements)

References 74 publications

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“…The inhibitory tumor microenvironment in ovarian cancer, including the highly suppressive ascitic microenvironment, 93 is an important obstacle that needs to be addressed for CAR T cells to be successful in this disease. One approach is to armor the CAR T cells with soluble cytokines, such as IL-12, 21 a proinflammatory cytokine that has been shown to enhance the cytotoxic capability of effector T cells 94 and to reprogram dendritic cells and myeloid-derived suppressor cells.…”

Section: Ovarian Cancermentioning

confidence: 99%

Adoptive T-Cell Therapy for Solid Tumors

Yeku¹,

Li²,

Brentjens³

2017

American Society of Clinical Oncology Educational Book

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OVERVIEW Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of immunotherapy wherein autologous T cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and various costimulatory molecules. Upon administration, these modified T cells traffic to, and recognize, cancer cells in an HLA-independent manner. CAR T-cell therapy has shown remarkable success in the treatment of CD-19–expressing B-cell acute lymphocytic leukemia. However, clinical gains to the same magnitude have not been reported in solid tumors. Several known obstacles to CAR T-cell therapy for solid tumors include target antigen identification, effective trafficking to the tumor, robust activation, proliferation, and in vivo cytotoxicity. Beyond these T-cell intrinsic properties, a complex and dynamic immunosuppressive tumor microenvironment in solid tumors hinders T-cell efficacy. Notable advancements in CAR design to include multiple costimulatory molecules, ligands, and soluble cytokines have shown promise in preclinical models, and some of these are currently in early-phase clinical trials. In this review, we discuss selected solid tumor malignancies and relevant preclinical data and highlight clinical trial results that are available. Furthermore, we outline some obstacles to CAR T-cell therapy for each tumor and propose strategies to overcome some of these limitations.

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Section: Ovarian Cancermentioning

confidence: 99%

Adoptive T-Cell Therapy for Solid Tumors

Yeku¹,

Li²,

Brentjens³

2017

American Society of Clinical Oncology Educational Book

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“…For these reasons, 5% dextrose infused simultaneously with paracentesis has been advocated. Possible complications of this method also include hypoproteinemia, hypotension, secondary peritonitis, perforation, and pulmonary embolism [95,96]. In order to prevent possible complications and homeostatic imbalance, it is necessary to perform blood tests control, focusing on protein and electrolyte levels, and the catheter needle should not stay in one site longer than 24 hours.…”

Section: Therapeutic Approach For the Patients With Ascitesmentioning

confidence: 99%

“…However, the application of shunts is indicated only for patients who cannot benefit from any other treatment and who can profit from it if their life expectancy is long enough. The median survival ranged in the different studies from 52 to 266 days, reflecting the high heterogeneity of patients, and possible fatal complications are pulmonary edema or emboli [96,108].…”

Section: Therapeutic Approach For the Patients With Ascitesmentioning

confidence: 99%

Ascitic Fluid in Ovarian Carcinoma – From Pathophysiology to the Treatment

Živadinović¹,

Petrić²,

Krtinić³

et al. 2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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Due to low symptomatology, a lack of screening, and relatively complicated diagnostic procedures of ovarian carcinoma, more and more women are believed to visit their doctors in advanced stage of the disease, complicated with ascitic fluid. There is an increasing evidence that peritoneal cytology is a subjective assessment with certain percentage of false-positive and false-negative results that may cause application of unnecessary chemotherapy or nonapplication of necessary chemotherapy. Maximal cytoreductive surgery followed by intraperitoneal or systemic chemotherapy remains to be the gold standard in preventing ascites. Ascites is not only a symptom of a disease, but a specific microenvironment for formation and mediation of protumorigenic signals that control ovarian cancer progression, proliferation, invasion, anti-apoptosis, chemoresistance and tumor heterogeneity. Acellular cytokines and immunological factors influence ovarian cancer progression and its ability to prevent immune responses of the body and tumor reaction to chemotherapy. Ascites contributes to disease dissemination, changing its course and final outcomes. Management of patients with ascites and ovarian carcinoma is complex and often the goal of the treatment is to target palliative procedures. Multidisciplinary approach is necessary in the management of these patients. Further investigations of new drugs and immunomodulators are needed aiming at prolonged periods between relapses.

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“…The heterogeneity in ascites constituents and their relative concentrations is exemplified by the presence of both oncogenic and tumor suppressive factors. In HGSC, ascites promotes tumor invasiveness and survival and inhibits apoptosis leading to chemoresistance . Along with the high protein concentration, increased inflammatory cytokines and chemokines and reduced lymphatic flow also contribute to the buildup of ascitic fluid and maintenance of an immunosuppressive TME that impairs the functions of innate and adaptive immune responses .…”

Section: Introductionmentioning

confidence: 99%

“…In HGSC, ascites promotes tumor invasiveness and survival and inhibits apoptosis leading to chemoresistance. 92 Along with the high protein concentration, increased inflammatory cytokines and chemokines and reduced lymphatic flow also contribute to the buildup of ascitic fluid and maintenance of an immunosuppressive TME that impairs the functions of innate and adaptive immune responses. 89,93,94 Ascites is rich in bioactive lipids as lysophosphatidic acid (LPA), that has been long identified as an OvCa promoting factor.…”

mentioning

confidence: 99%

Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

et al. 2018

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Ovarian cancer is the fifth most common cancer affecting women and at present, stands as the most lethal gynecologic malignancy. The poor disease outcome is due to the nonspecific symptoms and the lack of effective treatment at advanced stages. Thus, it is of utmost importance to understand ovarian carcinoma through several lenses and to dissect the role that the unique peritoneal tumor microenvironment plays in ovarian cancer progression and metastasis. This review seeks to highlight several determinants of this unique tumor microenvironment, their influence on disease outcome and ongoing clinical trials targeting these determinants.

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Ascites modulates cancer cell behavior, contributing to tumor heterogeneity in ovarian cancer

Cited by 144 publications

References 74 publications

Adoptive T-Cell Therapy for Solid Tumors

Adoptive T-Cell Therapy for Solid Tumors

Ascitic Fluid in Ovarian Carcinoma – From Pathophysiology to the Treatment

Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

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