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Tumor microenvironment and the importance of anti-tumor immunity for clinical course of human cancers
Partlová, Simona ; Špíšek, Radek (advisor) ; Drbal, Karel (referee) ; Kovář, Marek (referee)
Cancer development and progression vary depending on tumor type, localization, invasion, immunogenicity and the ability of immune system to become activated. There are frequent interactions between tumor cells and immune cells, occuring locally at the site of primary tumor or distally through paracrine signalling of various mediators and cytokines. The main subject of this PhD thesis is to study key factors and aspects of immune response in cancer patients. In the first part, we analyzed immune cells infiltrating tumor tissues of ovarian cancer patients at different stages of disease. We focused on the dynamics of immune response, primarily on frequency of individual T lymphocyte populations in peripheral blood and tumor infiltrating T lymphocytes in tumors of early and advanced stages of ovarian cancer. We found that during disease progression there is a gradual decrease of proinflammatory Th17 and Th1 immune responses and a specific recruitment of regulatory T cells to the tumor site, which results in a significant immune suppression in the tumor microenvironment. In the second part, we demonstrated that the character of immune response in HPV-positive head and neck cancer patients is very different from the patients with tumors not associated with HPV infection. In HPV-positive patients, significantly...
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Tumor microenvironment and the importance of anti-tumor immunity for clinical course of human cancers
Partlová, Simona ; Špíšek, Radek (advisor) ; Drbal, Karel (referee) ; Kovář, Marek (referee)
Cancer development and progression vary depending on tumor type, localization, invasion, immunogenicity and the ability of immune system to become activated. There are frequent interactions between tumor cells and immune cells, occuring locally at the site of primary tumor or distally through paracrine signalling of various mediators and cytokines. The main subject of this PhD thesis is to study key factors and aspects of immune response in cancer patients. In the first part, we analyzed immune cells infiltrating tumor tissues of ovarian cancer patients at different stages of disease. We focused on the dynamics of immune response, primarily on frequency of individual T lymphocyte populations in peripheral blood and tumor infiltrating T lymphocytes in tumors of early and advanced stages of ovarian cancer. We found that during disease progression there is a gradual decrease of proinflammatory Th17 and Th1 immune responses and a specific recruitment of regulatory T cells to the tumor site, which results in a significant immune suppression in the tumor microenvironment. In the second part, we demonstrated that the character of immune response in HPV-positive head and neck cancer patients is very different from the patients with tumors not associated with HPV infection. In HPV-positive patients, significantly...
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Immunotherapy of ovarian carcinoma with dendritic cells
Partlová, Simona ; Rožková, Daniela (advisor) ; Froňková, Eva (referee)
V ANGLICKÉM JAZYCE Immunotherapy of ovarian carcinoma with dendritic cells Anticancer immunotherapy is a therapeutical strategy aimed at elicitation and maintenance of immune responses against cancer cells. In this study we have focused on immunotherapy of ovarian cancer, because it is one of the most common gynaecological tumors with poor prognosis and high mortality. Our immunotherapy protocol involves preparing dendritic cells (DC) from monocytes isolated from patient's peripheral blood, which are subsequently pulsed with irradiated cells of established ovarian cancer cell line. These immature pulsed DC are maturated and subsequently co-cultivated with autologous T lymphocytes. The aim of this study was to demonstrate, that DC are able to elicit specific immune response after addition of suitable mature agens in combination with apoptotic ovarian tumor cells. Our observations indicate that 24 hours are sufficient for induction of tumor cells apoptosis. Additionally, we have shown that DC successfully ingested most of the apoptotic tumor cells after 4 hours of co-incubation. Furthermore, we have found out that ingestion of apoptotic cells by dendritic cells, which are stimulated with polyI:C, inhibits maturation of DC and consequently also production of cytokines IL-12p70, IL-6 and TNF-α. Whereas...
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Clostridium difficile - Importance and current options of laboratory diagnostics
Partlová, Simona ; Nyč, Otakar (advisor) ; Bártová, Markyta (referee)
This thesis mainly describes the question of Clostridium difficile diagnostic service. The first part briefly describes the characteristic of this bacterium. Further, the paper outlines common properties of the bacterium, the causes and manifestations of the diseases that it implicates and current opportunities of the laboratory service. The practical part of bachelors work deals with examination of toxin detection C.difficile in stool specimens, which was in case of positive result completed by cultivation. The cultivation and following Antimicrobial Susceptibility Testing (AST) is not routine task carried out in every clinical laboratory. PCR ribotyping is relatively new method that is provided rarely on the present. Generally, 195 patients have been tested in laboratory of Department of Medical Microbiology in Motol for Clostridium difficile toxin inherency in stool. Overall 30 samples have been tested as positive. The positive samples have been cultivated on special soil just for Clostridium difficile to acquire a clean culture. After that, the metronidazole susceptibility has been obtained from these gained isolates. Powered by TCPDF (www.tcpdf.org)
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