Tmic-19. knockdown of tumor-derived osteopontin/spp1 or application of a blocking peptide restores anti-tumor responses in experimental rat gliomas
Malignant glioma produced factors that attract and re-program microglia and infiltrating peripheral macrophages into proinvasive, immunosuppressive cells. This creates immunosuppressive milieu and inhibits responses of infiltrating T cells. Recently, we identified glioma-processed osteopontin/Spp1 as a major microglia-activating factor. Spp1 is a small glycoprotein, interacting via a RGD motif with integrin receptors on immune cells and via a CD44 binding domain with a CD44 on tumor cells. Tumor-processed Spp1 induces the pro-invasive re-programming of microglia in vitro. Knockdown of Spp1 in C6 glioma inhibits growth of i...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kaminska, B., Gieryng, A. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-18. role of microglia in the early steps of the brain metastatic cascade
In conclusion, our data suggest a step-dependent critical role of BMIC/microglia interactions during the brain metastatic cascade, and also provide a model to investigate the potential of microglia-directed therapies for BM prevention. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Berghoff, A., Feinauer, M., Solecki, G., Grosch, J., Osswald, M., Gil, B., Wilhelm, D., Raiky, U., Hainfellner, J., Steeg, P., Birner, P., Preusser, M., Wick, W., Winkler, F. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-17. subtype-specific cellular composition of the glioblastoma microenvironment
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, which has a dismal prognosis in spite of an aggressive, multi-modal treatment regimen. The Cancer Genome Atlas has identified four major subtypes based on distinct genetic signatures. These subtypes are referred to as proneural, neural, mesenchymal, and classical based on their associations with diverse neural cell lineages. The mesenchymal subtype, for example, shows enrichment of immune response-related genes and an association with tumor-associated macrophages (TAMs). TAMs have been shown to promote GBM growth and progression and, along ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kaffes, I., Szulzewsky, F., Alikhanyan, K., Herting, C., Shelton, J., Uhrbom, L., Nilsson, K. F., Nelander, S., Westermark, B., Huse, J., Holland, E., Brat, D., Hambardzumyan, D. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-16. tumor-infiltrating myeloid cells mediate adaptive immune resistance in glioblastoma
In this study, we identified a tumor-infiltrating Ly6-C+ CD11b+ myeloid (TIM) cell population that expands in response to DC vaccine treatment and significantly expresses PD-L1 in both our murine model and patient GBM samples. We hypothesized that this cell population is dominantly responsible for mitigating the immune response. To evaluate this, we administered tumor lysate-pulsed DC vaccine treatment to mice bearing intracranial murine GL261 tumor. Mice were randomized into treatment groups receiving PD-1 mAb, Ly6-C depleting mAb, or both. Following treatments, we euthanized mice and harvested tumor-bearing brain hemisph...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Antonios, J., Soto, H., Everson, R., Orpilla, J., Shin, N., Moughon, D., Sedighim, S., Treger, J., Odesa, S., Tucker, A., Yong, W., Cloughesy, T., Prins, R., Liau, L. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-15. mutant idh1 suppresses the procoagulant and promalignant effects of tissue factor in gliomas
Gliomas are one of the cancers most at risk of causing life-threatening venous thromboemboli (VTE). Previously, we discovered that gliomas with mutations in isocitrate dehydrogenase (IDH1mut) are much less likely to contain intratumoral microthrombi, and are much less likely to cause peripheral VTE, compared to IDH1 wild-type (IDH1wt) gliomas. We also found that IDH1mut gliomas have methylation-associated suppression of Tissue Factor (TF), a key initiator of thrombosis. Furthermore, prior studies have shown that TF directly increases the malignancy of many cancers through multiple transmembrane signaling pathways. In the c...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Unruh, D., Mirkov, S., James, C. D., Horbinski, C. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-13. quantitative analysis on the isolation of tumor mesenchymal stem-like cells from high grade gliomas
Tumor mesenchymal stem-like cells (tMSLCs) can be isolated from high grade gliomas and also play a role in a glioma progression as a participant in the tumor microenvironment. tMSLCs were known to have an effect on the overall survival of primary glioblastoma patients. However, Isolation rate of tMSLCs from surgical specimen was inconstant and the yield was not guaranteed. With a presumption that a relationship might exists between the weight of the sample and the yield rate, we assessed fifty-one fresh high grade glioma specimens and allocated them into two groups by the success or failure of isolation of the cells. As a ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Yoon, S.-J., Kong, S. H., Lee, J.-H., Moon, S., Oh, J., Sung, K. S., Kim, S. H., Park, S., Shim, J.-K., Moon, J. H., Park, J., Kim, E. H., Kim, S. H., Lee, S.-J., Huh, Y.-M., Park, S. W., Chang, J. H., Kang, S.-G. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-12. tmz results in priming of host immunity and changes in gbm tumor pdl-1 expression in a dose dependent fashion that can be leveraged for combination with immune checkpoint blockade
In this study, we hypothesised that dose modified TMZ improves GBM response to immune check point blockade by priming host immunity and changing tumor microenvironment. Murine glioma cell lines were treated with TMZ and checked for PD-1, PDL-1. mice were injected with different doses of TMZ to evaluate PD-1, PDL-1 in lymphocytes at different time points post TMZ. mice recieved OT- 1 splenocytes pre and post TMZ to determine effects of TMZ on antigen specific T cell recovery. GL-261 and GL-261 overexpressing MGMT (GL-MGMT) were implanted intracerebrally to mice and treated with PD-1 blockade and TMZ for survival study....
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Karachi, A., Azari, H., Flores, C., Yang, C., Dastmalchi, F., Mitchell, D., Rahman, M. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-11. hfe genotype alters exosome profiles in cancer
Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. A major focus in cancer biology is the impact of exosomes on metastasis and the microenvironment. The major goal of this study was to determine if changes in HFE genotype, associated with aggressive cancer phenotype, have significant effects on exosome profile. HFE, the most common autosomal recessive polymorphism in the Caucasian population, originally associated with hemochromatosis, is also associated with increased tumor burden, therapeutic resistance boost, and negative impac...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Mrowczynski, O., Madhankumar, A. Tags: TUMOR MICROENVIRONMENT Source Type: research
TMIC-10. AN IL-1{beta}/IL-1R PRO-TUMORIGENIC SIGNALING LOOP IN GLIOBLASTOMA
Glioblastoma (GBM) is the most aggressive and lethal malignant primary brain tumor in adults, with a high degree of intratumoral heterogeneity at both the cellular and molecular levels. The Cancer Genome Atlas (TCGA) project divided GBM into the proneural (PN), neural, classical, and mesenchymal (MES) subtypes based on distinct gene expression patterns. A further layer of complexity in GBM emerges from the tumor microenvironment in which these tumor cells develop and grow. The GBM microenvironment is composed of a wide variety of non-neoplastic stromal cells, including the vasculature, various infiltrating and residen...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Kaluzova, M., Gutmann, D., Hambardzumyan, D. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-09. expression analysis of idh1 wild-type and mutant glioma stem cells under hypoxia identifies novel survival-associated genes in glioblastoma patients
CONCLUSION:Taken together this study suggests, that IDH1mut GSCs do not seem to react to hypoxia on the transcriptional level. In contrast, IDH1wt GSCs regulate 34 genes, of which three show a significant survival correlation in GBM IDHwt patients. (Source: Neuro-Oncology)
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Trong, P. D., Warta, R., Geisenberger, C., Mairbäurl, H., Pusch, S., Unterberg, A., Herold-Mende, C. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-08. glioblastoma-induced astrocyte reprogramming generates a positive feedback loop to glioblastoma cells
Gliomas are lethal primary brain tumors inherently resistant to therapy. Several reports suggest a role for a stromal involvement in the progression of these tumors. We have previously isolated tumor associated astrocytes (TAGs) from mouse models of primary glioblastoma. We show for the first time that TAGs have a different gene expression profile from primary glial cells from mice without tumors. TAGs upregulate angiogenic factors and reprogramming factors like SOX2 and POU3F2 as well as Nestin and PDGFRa, normally expressed in neuronal precursors and oligodendrocyte precursors, respectively. Moreover, when isolated by FA...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Nilsen, M. H., Leiss, L. W. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-06. identity and gene profile of tumor-associated macrophages in glioblastoma
Glioblastoma (GBM) is the most aggressive and common type of brain tumor in adults, with patient survival times of approximately one year following diagnosis. The GBM microenvironment is composed of numerous non-neoplastic cells, including vascular endothelia, various infiltrating and resident immune cells, and non-neoplastic glial cells. The most abundant non-neoplastic cell population in the GBM microenvironment is tumor-associated macrophages (TAMs). TAMs comprise mixed populations of myeloid cells, including infiltrating macrophages from the blood circulation and resident brain microglia. TAMs are recruited to the GBM ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Chen, Z., Feng, X., Nie, K., Pong, W. W., Rasmussen, R., Gutmann, D., Hambardzumyan, D. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-05. fstl1, a marker for peritumoral brain edema and prognosis in glioma
Follistatin-like 1 (FSTL1), encoding a protein similar to follistatin, belongs to the SPARC (the secreted protein, acidic, rich in cysteine) family. In previous studies, FSTL1 was upregulated in glioblastoma and coexpression of FSTL1 with p53 was associated with poor survival of patients with glioblastoma multiformes (GBM). Here we report that, in glioma, FSTL1 promoted cell proliferation, invasion, migration and peritumoral brain edema (PTEB). It not only activated membrane receptor-DIP2A(disco interacting protein 2 homolog A) but also prevented nuclear translocation of DIP2A by competitive binding to DIP2A. A portio...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: You, Y. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-03. imaging brain tumor-associated neuroinflammation in animal models using ferumoxytol
In the brain tumor microenvironment, non-neoplastic cells with inflammatory function such as tumor-associated macrophages can influence the survival, proliferation and infiltrative activity of cancer cells. The ultrasmall superparamagnetic iron oxide nanoparticle, ferumoxytol, can be used as a contrast agent for magnetic resonance imaging (MRI) of brain vasculature, intracerebral tumors and neurological lesions. Although ferumoxytol is a blood pool agent immediately after infusion, we have shown that by 24h ferumoxytol leaks across the damaged blood-brain barrier in a rat model of acute neuroinflammation, where MRI signal ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Muldoon, L., Schwartz, D. Tags: TUMOR MICROENVIRONMENT Source Type: research
Tmic-02. targeting carcinoma-astrocyte gap junctions in brain metastasis
We have recently demonstrated that brain metastatic breast and lung cancer cells assemble carcinoma–astrocyte gap junctions composed of connexin 43 (Cx43) to engage with the astrocyte gap-junctional network. We found that brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-α (IFNα) and tumor necrosis factor (TNF). As paracrine signals, these factors activate the STAT1 and NF-B pathways in brain metastatic cells, thereby supporting tumor growth and chemoresistance. We ...
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Boire, A., Chen, Q., Daras, M., Kaley, T., Patel, K., DeAngelis, L., Massague, J. Tags: TUMOR MICROENVIRONMENT Source Type: research
