apyrase and Ascites

Ovarian cancer is the most lethal gynecological malignancy, with serous histotype as the most prevalent epithelial ovarian cancer (EOC). Peritoneal ascites is a frequent comorbidity in advanced EOC. EOC-associated ascites provide a reliable sampling source for studying lymphocytes directly from tumor environment. Herein, we carried out flow cytometry-based analysis to readdress issues on NK and T lymphocyte subsets in women with advanced EOC, additionally evaluating phenotypic modulation of their intracellular pathways involved in interleukin (IL)-2 and IL-15 signaling. Results depicted ascites as an inflammatory and immunosuppressive environment, presenting significantly (

Topics: Adult; Aged; Aged, 80 and over; Apyrase; Ascites; CD56 Antigen; Cystadenocarcinoma, Serous; Female; Gene Expression Regulation, Neoplastic; Humans; Immunophenotyping; Interleukin-10; Interleukin-15; Interleukin-2; Interleukin-6; K562 Cells; Killer Cells, Natural; Middle Aged; Neoplasm Grading; Neoplasm Staging; Ovarian Neoplasms; Programmed Cell Death 1 Receptor; Signal Transduction; STAT5 Transcription Factor; T-Lymphocytes; Tumor Microenvironment

Ovarian cancer is a prevalent gynecological malignancy with potent immune-suppression capabilities; regulatory T cells (Tregs) are significant contributors to this immune-suppression. As ovarian cancer patients present with high levels of TNF and Tregs expressing TNFR2 are associated with maximal suppressive capacity, we investigated TNFR2+ Tregs within these patients. Indeed, TNFR2+ Tregs from tumor-associated ascites were the most potent suppressor T cell fraction. They were abundantly present within the ascites and more suppressive than peripheral blood TNFR2+ Tregs in patients. The increased suppressive capacity can be explained by a distinct cell surface expression profile, which includes high levels of CD39, CD73, TGF-β and GARP. Additionally, CD73 expression level on TNFR2+ Tregs was inversely correlated with IFN-γ production by effector T cells. This Treg fraction can be selectively recruited into the ascites from the peripheral blood of patients. Targeting TNFR2+ Tregs may offer new approaches to enhance the poor survival rates of ovarian cancer.

Topics: 5'-Nucleotidase; Aged; Antigens, CD; Apyrase; Ascites; CTLA-4 Antigen; Cytokines; Female; Forkhead Transcription Factors; GPI-Linked Proteins; Humans; Leukocytes, Mononuclear; Membrane Proteins; Middle Aged; Ovarian Neoplasms; Receptors, Tumor Necrosis Factor, Type II; T-Lymphocytes, Regulatory; Tumor Microenvironment

The mechanism leading to the hypercoagulability in pancreatic carcinoma is unclear. The rapid progress of the disease after its diagnosis and the inaccessibility of the tumor make studies on the mechanism difficult in man. With the successful induction of this malignancy and conversion of it into an ascites tumor in Syrian golden hamsters, interactions between isolated tumor cells and individual hemostatic components can be investigated. In this paper, studies on in vitro tumor cell-platelet interactions and some hemostatic changes in hamsters following intravenous injection of isolated tumor cells are described. Freshly isolated tumor cells and tumor-cell sonicates, but not those that had been kept at 4 or -70 C overnight, induced comparable aggregation of human platelets in both heparinized and citrated platelet-rich plasmas (hPRP and cPRP). The aggregation was not followed by clot formation; a specific synthetic thrombin inhibitor had no effect on the aggregation in either hPRP or cPRP. Washed and gel-filtered platelets, even in the presence of 5% of citrated or heparinized platelet-poor plasma (cPPP or hPPP) failed to be aggregated by tumor cells. Tumor-cell-induced platelet aggregation was accompanied by thromboxane formation and serotonin release, both of which were several orders of magnitude greater in cPPP than in hPRP. Aspirin, apyrase, and PGI2 all inhibited tumor-cell-induced platelet aggregation in both PRPs, but the inhibition by aspirin was minimal. Intravenous infusion of isolated tumor cells into normal hamsters resulted in a 50% reduction of platelet count and a 20-30% decline in antithrombin III and fibrinogen. Platelet aggregates and fibrin strands were seen in the lungs of these animals.

Topics: Animals; Antithrombin III; Apyrase; Ascites; Aspirin; Blood Coagulation; Blood Platelets; Cricetinae; Epoprostenol; Fibrinogen; Humans; Mesocricetus; Microscopy, Electron; Pancreatic Neoplasms; Platelet Aggregation; Platelet Count; Serotonin; Thromboxane B2