![]() These findings support our hypothesis that sEV-pGSN attenuates immunosurveillance and regulates GSH biosynthesis, a phenomenon that contributes to chemoresistance in ovarian cancer. IFN$\gamma$ secretion was therefore reduced, resulting in high GSH production and resistance to CDDP-induced death in ovarian cancer cells. ![]() In chemoresistant conditions, increased secretion of sEV-pGSN by ovarian cancer cells induced apoptosis in CD8 T cells. This resulted in increased T-cell secretion of IFN$\gamma$, which reduced intracellular glutathione (GSH) production and sensitized chemosensitive cells to cis-diaminedichloroplatinum (CDDP)-induced apoptosis. In chemosensitive conditions, secretion of sEV-pGSN was low, allowing for optimal CD8 T-cell function. Here, we report the immunomodulatory roles of sEV-pGSN in ovarian cancer chemoresistance. Plasma gelsolin (pGSN) is transported by exosomes (small extracellular vesicle, sEV) and plays a key role in ovarian cancer chemoresistance, yet little is known about its role in immunosurveillance. Because of poor infiltration of effector T cells, patients are mostly unresponsive to immunotherapy. (p<0.0006 for ImmunoCult™-XF T Cell Expansion Medium versus all other serum-supplemented media except for Competitor 4, tested using the linear mixed effect model with linear regression, n = 1 to 19 donors).Īlthough initial treatment of ovarian cancer is successful, tumors typically relapse and become resistant to treatment. Each column with error bars represents the mean ± S.E.M. Competitors 1 to 4 represent serum-supplemented competitor media, which include, in no particular order, X-VIVO™ 15 serum, CTS™ OpTmizer™ T Cell Expansion SFM serum, RPMI 1640 serum, and IMDM serum. (B) Compared to all serum-supplemented competitor media tested, ImmunoCult™-XF T Cell Expansion Medium showed similar or significantly higher expansion of total T cells. (p<5x10 -13 for ImmunoCult™-XF T Cell Expansion Medium versus all other serum-free media, tested using the linear mixed effect model with linear regression, n = 4 to 19 donors). Competitors 1 to 6 represent serum-free competitor media, which include, in no particular order, X-VIVO™ 15 (Lonza), AIM V® Medium (Life Tech), CellGro® DC Medium (CellGenix), CTS™ OpTmizer™ T Cell Expansion SFM (Life Tech), TexMACS™ Medium (Miltenyi), and PRIME-XV® T Cell Expansion XSFM (Irvine Scientific). (A) Compared to all serum-free competitor media tested, ImmunoCult™-XF T Cell Expansion Medium showed significantly higher expansion of total T cells. T cells were analyzed on day 21 for fold expansion relative to the initial cell seeding density. T cells were stimulated with ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator on day 0 and every 7 to 8 days for the duration of the culture. ![]() T cells were isolated from human peripheral blood samples using the EasySep™ Human T Cell Isolation Kit (Catalog #17951), stimulated with ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator (Catalog #10970), and cultured in (A) ImmunoCult™-XF T Cell Expansion Medium or serum-free competitor media with rhIL-2 in three replicate cultures per donor, or cultured in (B) ImmunoCult™-XF T Cell Expansion Medium or serum-supplemented competitor media with rhIL-2 in three replicate cultures per donor. ImmunoCult™-XF T Cell Expansion Medium Supports Greater T Cell Expansion Than Other Serum-Free and Serum-Supplemented Media The average fold expansion of T cells in ImmunoCult™-XF T Cell Expansion Medium were 15-fold on day 7, 80-fold on day 10, 450-fold on day 14, and 4,000-fold on day 21.įigure 2. at the specified time points (p<0.05 for ImmunoCult™-XF versus all media for days 8, 11, 14, 18, and 21, tested using two-tailed, paired t-test with unequal variance, n = 6 to 19 donors). ![]() Each data point represents the mean fold expansion ± S.E.M. Competitors 1 to 4 include, in no particular order, X-VIVO™ 15 (Lonza), AIM V® Medium (Life Tech), CellGro® DC Medium (CellGenix), and RPMI 1640 serum. Compared to all competitor media tested, ImmunoCult™-XF T Cell Expansion Medium showed significantly higher expansion of total T cells. T cells were analyzed on days 4, 7, 8, 10, 11, 14, 18, and 21 for fold expansion relative to the initial cell seeding density. T cells were isolated from human peripheral blood samples using the EasySep™ Human T Cell Isolation Kit (Catalog #17951), stimulated with ImmunoCult™ Human CD3/CD28/CD2 T Cell Activator (Catalog #10970), and cultured in ImmunoCult™-XF T Cell Expansion Medium supplemented with rhIL-2. ImmunoCult™-XF T Cell Expansion Medium Supports Faster T Cell Expansion Than Other Serum-Free and Serum-Supplemented Media
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