Ontology highlight
ABSTRACT:
PROVIDER: PRJNA773599 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin)
| PRJNA773260 | ENA
Project description:Goal: determine how transcriptome of immune cells within the tumor microenvironment changes as a function of CD40 agonist and/or immune checkpoint blockade (anti-PD-1 AND anti-CTLA-4; "ICB") therapy
2020-05-10 | GSE150176 | GEO
Project description:Immune checkpoint blockades (ICBs) have been approved for treating multiple cancer types, but the response rate is limited for many solid tumors. Much efforts have been devoted to understand the mechanisms governing ICB therapy efficacy and the abundance of tumor-infiltrating lymphocytes is among the factors that influence on ICB responsiveness. The deubiquitinase TRABID was identified in our previous study as a positive regulator of autophagy by stabilizing VPS34, the class III PI3K critical for autophagosome formation. In this study, we identify an upregulation of TRABID in mitosis and its critical role in mitotic progression through deubiquitination and stabilization of AURKB and BIRC5, two subunits of the chromosome passenger complex governing multiple mitotic steps. Furthermore, TRABID depletion induces micronuclei phenotype, which is likely mediated by the combinatory defects in mitosis and autophagy. Consequently, TRABID depletion or inhibition activates cGAS/STING pathway to induce type I interferon production and inflammatory responses. TRABID depletion in tumors cells reduces tumor burden and promotes anti-tumor immune surveillance by increasing tumor infiltration of CD4+ and CD8+ T cells and NK cells and reducing Treg cells. Clinically, TRABID expression in multiple cancer types correlates negatively with the infiltration of anti-tumor immune cells and positively with that of pro-tumor immune cells. Our study supports a suppressive role of tumor-intrinsic TRABID in anti-tumor immunity and suggests TRABID inhibitor as a promising agent for enhancing the sensitivity of solid tumors to ICB therapy.
2023-05-11 | PXD035002 | Pride
Project description:We generated immune checkpoint blockade resistant cell lines from a prostate tumor driven by Probasin-Cre Pten/P53/Smad4 loxp deletion, through serial implantation and ICB treatment. We then wanted to explore whether gene expression changes associated with resistance to immune checkpoint blockade could be reversed by treating ICB resistant cells with the pan-HDAC inhibitor Vorinostat. We used a microarray to determine gene expression changes caused by Vorinostat treatment in these cells with biological duplicates.
2024-02-13 | GSE205469 | GEO
Project description:While mitotic spindle inhibitors specifically kill proliferating tumor cells without the toxicities of microtubule poisons, resistance has limited their clinical utility. Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of STAT3. Furthermore, these senescent cells expand the repertoire of resistant cells by secreting an array of factors, including TGFb, which induce proliferating cells to exit mitosis and become quiescent—a state that is also insensitive to spindle inhibitors. Targeting STAT3 restores sensitivity to each of these drugs by depleting the senescent subpopulation and inducing quiescent cells to enter the mitotic cycle. We have incorporated our results into a model that explains how STAT3 and therapy induced senescence combine to drive resistance, which can provide insight into how to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma.
2024-10-28 | GSE267458 | GEO
Project description:Non-inflamed (cold) tumors such as leiomyosarcoma (LMS) do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis-, or poly-ADP ribose polymerase (PARP) inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pre-treated LMS patients.
2024-01-01 | E-MTAB-12922 | biostudies-arrayexpress
Project description:drugs targeting mitosis might affect the tumor microenvironment and sensitize cancer cells to immunotherapy. BAL101553 monotherapy increased survival in immune checkpoint blockade–resistant SB28 glioblastoma tumors and synergized with anti-CD40 antibody
2021-10-23 | GSE186302 | GEO
Project description:Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collected biopsies from a cohort of 44 melanoma patients after progression to anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways were observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions had a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and TCR clonality analyses. One anti-PD1 resistant lesion harbored a distinct immune cell niche, however, anti-PD1 resistant tumors were generally immune poor with non-expanded TCR clones. Such immune poor microenvironments were associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors had reduced fractions of PD1+ CD8+ T cells as compared to ICB naïve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination.
2024-02-06 | GSE244982 | GEO
Project description:Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collected biopsies from a cohort of 44 melanoma patients after progression to anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways were observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions had a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and TCR clonality analyses. One anti-PD1 resistant lesion harbored a distinct immune cell niche, however, anti-PD1 resistant tumors were generally immune poor with non-expanded TCR clones. Such immune poor microenvironments were associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors had reduced fractions of PD1+ CD8+ T cells as compared to ICB naïve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination.
2024-02-06 | GSE244983 | GEO
Project description:Yeast cell cycle transcript dynamics in three S. cerevisiae strains grown at 30 degrees Celsius: cdc20 GALL-CDC20 (persistent mitotic CDK activity; CDK on), cdc8-ts (DNA replication checkpoint), GAL-cse4-353 (spindle assembly checkpoint), cdc8-ts cdc20 (DNA replication checkpoint, CDK on), and cdc8-ts cdc20, rad53-1 (DNA replication checkpoint without Rad53 activity, CDK on) in a BF264-15DU background. We compared transcript levels of genes previously shown to be periodically expressed in wild-type cells and in cells lacking all mitotic cyclins (clb1,2,3,4,5,6; CDK off). Two replicate time courses for each of the strains studied are included
2014-07-27 | E-GEOD-49650 | biostudies-arrayexpress