Tumor FAK Orchestrates Immunosuppression in Ovarian Cancer via the CD155/TIGIT axis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA757619 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:An immune profiling of cells recovered from the peritoneal cavity of mice seeded with KMF ovarian cancer cells with FAK knockout reconstituted with FAK or a kinase dead FAK An immune profiling of cells recovered from the peritoneal cavity of mice seeded with KMF ovarian cancer cells with FAK kockout reconstituted with FAK, then treated with FAKi VS4716 (100mg/kg) or vehicle by gavage twice daily.
2022-06-15 | GSE182726 | GEO
Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses. TIGIT+ and TIGIT- Tregs were sorted from naïve Foxp3-GFP KI mice (pooled spleen and lymph nodes) TIGIT: T cell immunoreceptor with Ig and ITIM domains
2014-12-12 | E-GEOD-56299 | biostudies-arrayexpress
Project description:Gene copy number changes, cancer stem cell (CSC) increases, and platinum chemotherapy resistance contribute to poor prognosis in patients with recurrent high grade serous ovarian cancer (HGSOC). CSC phenotypes involving Wnt-b-catenin and aldehyde dehydrogenase activities, platinum resistance, and tumor initiating frequency are here associated with spontaneous genetic gains, including genes encoding KRAS, MYC and FAK, in a new murine model of ovarian cancer (KMF). Noncanonical FAK signaling was sufficient to sustain human and KMF tumorsphere proliferation, CSC survival, and platinum resistance. Increased FAK tyrosine phosphorylation occurred in HGSOC patient tumors surviving neo-adjuvant platinum and paclitaxel chemotherapy and platinum resistant tumorspheres acquired FAK dependence for growth. Importantly, combining a pharmacologic FAK inhibitor with platinum overcame chemoresistance and triggered apoptosis in vitro and in vivo. Knockout, rescue, genomic and transcriptomic analyses collectively identified more than 400 genes regulated along a FAK/b-catenin/Myc axis impacting stemness and DNA repair in HGSOC, with 66 genes gained in a majority of Cancer Genome Atlas samples. Together, these results support combinatorial testing of FAK inhibitors for the treatment of recurrent ovarian cancer.
2019-07-01 | GSE129098 | GEO
Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses.
2014-12-12 | GSE56299 | GEO
Project description:Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy. In this study, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups. We found that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME). In conclusion, TIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment.
2022-03-30 | GSE194209 | GEO
Project description:We compared the gene expression in wild type CD4+ T cells stimulated with agonistic anti-TIGIT 4D4 antibody to that of isotype and TIGIT-deficient (KO) controls.
2011-01-01 | E-MEXP-2847 | biostudies-arrayexpress
Project description:Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Although the application of immune checkpoint, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), achieved definite efficacy, the effect of immunotherapy for bladder cancer is still not very satisfactory. Therefore, it is very urgent to develop new targets to expand the options of immunotherapies. In this study, we utilized single cell sequencing to explore the cell composition and detected a subset of Treg cells with high expression of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and interleukin (IL)-32 molecules. Certainly, anti-tumor immune response was suppressed by this subset of Treg cells and IL-32 promoted the bladder cancer metastasis. Nevertheless, targeting TIGIT not only could reverse immunosuppression through restoring anti-tumor immune response mediated by T cells but suppressed the secretion of IL-32 and inhibited the metastasis of bladder cancer cells. Thus, our study provided a novel insight into the immunosuppression in bladder cancer and developed the TIGIT as the novel target for immunotherapy of bladder cancer. Furthermore, we also illustrated mechanism of the dual effect of targeting TIGIT in bladder cancer and revealed the metastasis-promoting effect of IL-32 in bladder cancer. Taken together, the discovery raises the possibility of TIGIT targets against bladder cancer from the bench to the bedside.
2022-01-31 | GSE186520 | GEO
Project description:The CD155/TIGIT axis can be co-opted during immune evasion in chronic viral infections and cancer. Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy, and immune-based strategies to combat this disease have been largely unsuccessful to date. We corroborate prior reports that a substantial portion of PDAC harbors predicted high affinity MHC class I-restricted neoepitopes and extend these findings to advanced/metastatic disease. Using two novel preclinical models of neoantigen-expressing PDAC, we demonstrate that intratumoral neoantigen-specific CD8+ T cells adopt multiple states of dysfunction, which are similar to tumor-infiltrating lymphocytes of human PDAC patients. Mechanistically, genetic and/or pharmacologic modulation of the CD155/TIGIT axis was sufficient to promote immune evasion in autochthonous neoantigen-expressing PDAC. Finally, we demonstrate that the CD155/TIGIT axis is critical to maintain immune evasion in PDAC and uncover a combination immunotherapy (TIGIT/PD-1 co-blockade plus CD40 agonism) that elicits profound anti-tumor responses in preclinical models, now poised for clinical evaluation.
2021-07-25 | GSE163059 | GEO
Project description:Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in proliferation, motility, adhesion, invasion, angiogenesis, and survival signaling. Focal adhesion kinase has been shown to be overexpressed in many types of tumors, including breast cancer at early stages of tumorigenesis. To study the biological role of FAK in breast tumorigenesis, we used FAKsiRNA to down-regulate FAK in MCF-7 cell lines.
2009-08-17 | GSE11581 | GEO
Project description:Gene copy number changes, cancer stem cell (CSC) increases, and platinum chemotherapy resistance contribute to poor prognosis in patients with recurrent high grade serous ovarian cancer (HGSOC). CSC phenotypes involving Wnt-b-catenin and aldehyde dehydrogenase activities, platinum resistance, and tumor initiating frequency are here associated with spontaneous genetic gains, including genes encoding KRAS, MYC and FAK, in a new murine model of ovarian cancer (KMF). Noncanonical FAK signaling was sufficient to sustain human and KMF tumorsphere proliferation, CSC survival, and platinum resistance. Increased FAK tyrosine phosphorylation occurred in HGSOC patient tumors surviving neo-adjuvant platinum and paclitaxel chemotherapy and platinum resistant tumorspheres acquired FAK dependence for growth. Importantly, combining a pharmacologic FAK inhibitor with platinum overcame chemoresistance and triggered apoptosis in vitro and in vivo. Knockout, rescue, genomic and transcriptomic analyses collectively identified more than 400 genes regulated along a FAK/b-catenin/Myc axis impacting stemness and DNA repair in HGSOC, with 66 genes gained in a majority of Cancer Genome Atlas samples. Together, these results support combinatorial testing of FAK inhibitors for the treatment of recurrent ovarian cancer.
2019-07-01 | GSE129097 | GEO