Download or read book Impact of the Glioma Microenvironment on Antitumor Immunity written by Valérie Dutoit and published by Frontiers Media SA. This book was released on 2022-01-31 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Brain Tumor Immunotherapy written by Linda M. Liau and published by Springer Science & Business Media. This book was released on 2000-11-10 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt: An authoritative panel of researchers and clinicians critically reviews the entire field to provide a comprehensive guide to modern brain tumor immunotherapy and thereby enhance future research in this area. The contributors detail many of the key laboratory experiments and clinical protocols that are currently being investigated, integrate the available information from previous and ongoing research, and help define the current status of the field. Topics range from adoptive cellular and antibody-mediated immunotherapy of brain tumors to tumor vaccines and related strategies, and include many vanguard experimental strategies and immunological techniques for studying brain tumor immunotherapy. Cutting-edge and comprehensive, Brain Tumor Immunotherapy brings together all the important recent advances in our understanding of central nervous system tumor immunology and illustrates in powerful detail the many new applications now harnessing the immune response for brain tumor therapeutics.
Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-08 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book focuses on the role of hematopoietic components of the tumor microenvironment. Further, it teaches readers about the roles of distinct constituents of the tumor microenvironment and how they affect cancer development. Topics include neutrophils, basophils, T helper cells, cytotoxic lymphocytes, fibrocytes, and myeloid-derived suppressor cells, and more. Taken alongside its companion volumes, these books update us on what we know about various aspects of the tumor microenvironment as well as future directions. Tumor Microenvironment: Hematopoietic Cells – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.
Download or read book CNS Cancer written by Erwin G. Van Meir and published by Springer Science & Business Media. This book was released on 2009-08-15 with total page 1294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancers of the central nervous system are among the most lethal of human neoplasms. They are recalcitrant to even intensive multimodality therapies that include surgery, radiotherapy, and chemotherapy. Moreover, especially in children, the consequences of these therapies can itself be devastating and involve serious cognitive and developmental disorders. It is small wonder that such cancers have come under the intense scrutiny of each of the subspecialties of clinical care and investigation as well as attracting some of the best basic research scientists. Their joint efforts are gradually peeling away the mysteries surrounding the genesis and progression of these tumors and inroads are being steadily made into understanding why they resist therapies. This makes it an especially opportune time to assemble some of the best investigators in the field to review the ‘‘state of the art’’ in the various arenas that comprise the assault on CNS tumors. The breadth of this effort by the clinical and basic neuro-oncology community is quite simply amazing. To a large extent, it evolves from the knowledge of the human genome and its regulation that has been hard won over the past two decades.
Download or read book Adult diffuse glioma microenvironment Insight into cancer ecology written by Aleksi Sedo and published by Frontiers Media SA. This book was released on 2023-03-29 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Effects of Neoadjuvant Anti Programmed Cell Death Protein 1 PD 1 Therapy on the Tumor Infiltrating T Cell Compartment and Tumor Microenvironment Immune Composition in Recurrent Glioblastoma Patients written by Alexander Hao Lee and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Glioblastoma (GBM) is the most common malignant tumor in the central nervous system and has poor patient survival rates. Unlike other cancers, immune checkpoint therapies, such as PD-1 checkpoint blockade, have been largely ineffective in GBMs for several reasons: an immunosuppressive tumor microenvironment, a lack of suitable neoantigens, and poor intratumoral T cell infiltration and activity. However, there is evidence that using anti-PD-1 therapy in the neoadjuvant setting may generate a more robust anti-tumor immune response, though characterizing how the GBM tumor microenvironment changes with such therapy is incomplete. As such, we performed high dimensional analysis using CyTOF mass cytometry and single-cell RNAsequencing to study the intratumoral immune populations in GBM patients treated with or without neoadjuvant anti-PD-1 therapy. Characterizing PD-1 expressing tumor infiltrating T cell populations showed that PD-1 was associated with markers of T cell activation and dysfunction regardless of treatment and that this association existed less strongly in peripheral PD-1 expressing T cells. We studied the effects of neoadjuvant anti-PD-1 therapy on a large patient cohort of tumor infiltrating immune cells and found that neoadjuvant anti-PD-1 therapy significantly increased the proportion of several intratumoral T cell sub-populations, including a TCF7-expressing progenitor exhausted population. Downstream effects of neoadjuvant anti-PD-1 therapy on T cells, namely increased production of IFN-g, included transcriptionally altering the myeloid and dendritic cell populations to be more immune suppressive but also potentially more vulnerable to other immune checkpoint therapies, specifically anti-TIGIT and anti-CTLA-4 therapies. Due to the impact of neoadjuvant anti-PD-1 therapy on intratumoral T cell populations, we examined whether we could detect tumor-reactive T cells by cloning TCRs from transcriptionally defined populations in a patient treated with neoadjuvant anti-PD-1 and testing reactivity to the patient-derived gliomasphereline. Among TCRs cloned, we discovered that T cells arising from the activated and exhausted population showed tumor reactivity, suggesting that utilizing transcriptional phenotypes can guide selection of potential tumor-reactive TCRs in GBM patients treated with neoadjuvant anti-PD-1 therapy. In conclusion, neoadjuvant anti-PD-1 therapies alters the immune landscape in these tumors and can be potentially used in combination with other immunotherapies to more effectively treat this malignancy.
Download or read book Gliomas microenvironment New drug entities mechanisms of action molecular biomarkers and drug delivery strategies written by Célia Cabral and published by Frontiers Media SA. This book was released on 2024-07-26 with total page 161 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gliomas are neoplasms originating in glial cells, the most malignant and frequent primary tumors of the Central Nervous System (CNS), representing approximately 40-50% of all intracranial tumors. Following the World Health Organization (WHO) guidelines, gliomas are classified into grades I-IV, regarding their malignancy degree. The latest report from WHO on CNS tumors considers that glioblastoma (GB), a grade IV adult-type diffuse glioma comprising isocitrate dehydrogenase (IDH)-wildtype tumors. Despite all efforts to improve patient survival and quality of life, the median survival remains lower due to the lack of effective diagnostic tools, poor prognosis, and limited therapeutic options. Regarding this, the design of novel treatment strategies is of the utmost importance. This can be by either the discovery of new medicines (for example synthetic compounds), repurposing known drugs or exploring novel strategies of drug delivery by nanotechnological platforms to improve treatment response and long-term survival of patients. Inter and intra-tumor heterogeneity mainly contribute to the poor prognosis and treatment efficacy. Therefore, exploiting tumor microenvironment (TME) and understanding GB’s cellular and molecular aspects are fundamental to developing more effective and better-tolerated personalized therapies. Thus, addressing physiological mechanisms involved in cancer development, progression and recurrence is crucial. Concerning this, our goal with this research topic is to share the latest advances in tumor-specific therapies for gliomas, especially GB, as well as to provide experimental validation of new bioactive molecules and their antitumor mechanism of action. Authors are invited to submit original research, review articles and systematic reviews covering, but not restricted to, the following topics: 1) Novel targeted therapies; 2) Mechanism of action and affected signaling pathways; 3) Repurposing drugs; 5) New chemical entities; 6) Pharmaceutical nanotechnology; 7) Drug delivery systems; 8) Preclinical and clinical studies of therapeutic molecules; 9) Potential molecular biomarkers to targeted therapies using proteomics or transcriptomics.
Download or read book Tumor Induced Immune Suppression written by Dmitry I. Gabrilovich and published by Springer Science & Business Media. This book was released on 2014-02-10 with total page 471 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor-Induced Immune Suppression - Prospects and Progress in Mechanisms and Therapeutic Reversal presents a comprehensive overview of large number of different mechanisms of immune dysfunction in cancer and therapeutic approaches to their correction. This includes the number of novel mechanisms that has never before been discussed in previous monographs. The last decades were characterized by substantial progress in the understanding of the role of the immune system in tumor progression. Researchers have learned how to manipulate the immune system to generate tumor specific immune response, which raises high expectations for immunotherapy to provide breakthroughs in cancer treatment. It is increasingly clear that tumor-induced abnormalities in the immune system not only hampers natural tumor immune surveillance, but also limits the effect of cancer immunotherapy. Therefore, it is critically important to understand the mechanisms of tumor-induced immune suppression to make any progress in the field and this monograph provides these important insights.
Download or read book Angiogenesis in Brain Tumors written by Matthias Kirsch and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: - Volume is divided into four sections, allowing easy navagation for researchers and practicing physicians - Text includes clinical trials - Written by leaders in the field
Download or read book Tumor Immunology and Immunotherapy written by Robert C. Rees and published by Oxford University Press, USA. This book was released on 2014 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor immunology and immunotherapy provides a comprehensive account of cancer immunity and immunotherapy. Examining recent results, current areas of interest and the specific issues that are affecting the research and development of vaccines, this book provides insight into how these problems may be overcome as viewed by leaders in the field.
Download or read book Neurosurgical Procedures written by Alba Scerrati and published by BoD – Books on Demand. This book was released on 2020-04-22 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the last few years, the development of new technologies in the medical field has allowed procedures and improved surgical techniques to be performed, which until recently would have been unthinkable.Modern neurosurgery is forever tied to technological progress: the development of robotics and robotic-assisted surgery; enhanced visualization, perfusion, and function monitoring in vascular surgery; new techniques of bone reconstruction; new cerebral imaging tools; and alternative treatments such as laser interstitial thermal therapy or immunotherapy for tumors. This book is designed to be a comprehensive introduction to these new developments and to their application in clinical practice. We have tried to provide a unique background and insights to coherently present these new technologies.
Download or read book Enhancing Immunity to Glioma Modulating the Adaptive Immune Response in the Tumor Microenvironment written by Joseph Paul Antonios and published by . This book was released on 2016 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Glioblastoma (GBM) is the most common and lethal of all adult primary malignant brain tumors. For patients diagnosed with GBM, the median survival is 11-14 months despite advances in surgical resection techniques, chemotherapies, and radiation therapy (1). Alternate therapeutic strategies are being actively pursued to target GBM, with various immunotherapeutic modalities designed to generate an anti-GBM immune response showing considerable promise in preclinical models and clinical trials. To more effectively target GBM with these treatments, there has been an increasing appreciation of the numerous mechanisms involved in generating and maintaining the highly immunosuppressive tumor microenvironment in recent years. These studies have described a variety of microenvironmental and systemic factors that promote glioma cell evasion from the immune system. In light of these, it has become apparent that these factors must be understood and explicitly targeted to mount a successful immune response against GBM. This thesis describes the utilization of two different immunotherapeutic strategies to target GBM. The first strategy created a novel GBM target by inducing NY-ESO-1 antigen expression with the demethylating agent, decitabine, and targeting that antigen with engineered T cells. Specifically, we utilized human GBM cell cultures to induce expression of the antigen. We evaluated NY-ESO-1 TCR-transduced T cell-mediated GBM tumor cytolysis in a series of in vitro cytotoxicity assays. Following this, we examined the application of this therapy using an intracranially-implanted xenograft model. Our studies demonstrated that decitabine could effectively upregulate NY-ESO-1 both in vivo and in vitro. Engineered T cells were able to induce tumor cytolysis in vitro and were able to traffic to and target tumor in vivo. Tumor-bearing mice receiving adoptive transfer of these engineered T cells demonstrated significantly increased survival over mice that received non-transduced T cells. By inducing expression of a novel target on GBM, we were able to generate a highly specific, anti-GBM immune response. This strategy represented a clinically translatable therapeutic technique for treating patients with GBM. The second strategy focused on using existing GBM targets to generate an endogenous immune response in a syngeneic, immune competent mouse model. Briefly, we administered an autologous tumor lysate-pulsed dendritic cell (DC) vaccine to produce a glioma-specific immune response. In our studies, the vaccination appeared to be capable of inducing T cell infiltration into tumors; however, in large, established tumors, this infiltrating response was not sufficient to increase mouse survival and provide significant therapeutic benefit. We described the role of the negative costimulatory pathway, programmed death-1/ligand-1 (PD-1/PD-L1) in mitigating T cell activation and memory in a series of in vitro and in vivo studies. We noted that PD-1 blockade with PD-1 mAb was not sufficient to produce a T cell infiltrate. However, when administered with DC vaccination, PD-1 blockade activated the vaccine-generated T cell response in the tumor microenvironment. We found that T cells with PD-1 mAb were able to mediate significant tumor cytolysis when compared to T cells without PD-1 blockade in vitro. The adjuvant administration of PD-1 mAb with the DC vaccine resulted in significant survival benefit over DC vaccine alone in mice bearing large, established gliomas. Additionally, this dual treatment resulted in the increased expression of integrin homing and immunologic memory markers on T cells infiltrating tumor. These findings were corroborated in samples from patient GBM, with PD-1 blockade enhancing the T cell-mediated GBM cytolysis. Concerning this strategy, then, these findings provided us with a means to both generate and enhance a tumor-specific response. While this second strategy proved effective, the mechanism underlying this PD-1/PD-L1-mediated suppression was not fully understood. As such, we proceeded to identify a PD-L1-expressing tumor infiltrating myeloid (TIM) cell population that appeared to dominantly regulate the PD-1/PD-L1 signaling mechanism. Importantly, we determined the role that these cells play in inhibiting the immune response using a series of in vitro and in vivo studies utilizing TIM depletion and PD-1 mAb treatment strategies. We found that depletion of TIMs in both human GBM cultures and murine glioma abolished PD-1/PD-L1-mediated inhibition of T cell activation. Targeting TIMs with colony stimulating factor-1 receptor inhibitor (CSF-1Ri) reduced the TIM population significantly and altered the remaining TIMs such that they demonstrated increased expression of chemotactic factors. While treatment with CSF-1Ri in conjunction with DC vaccine did not alter PD-L1 expression on remaining TIMs, we did note that there was increased TIL infiltration with this dual treatment significantly over DC vaccine alone. These findings suggested that TIMs exert inhibitory effects in the tumor microenvironment in a manner not restricted only to the PD-1/PD-L1 signaling mechanism. We found that the combined treatment of CSF-1Ri and PD-1 mAb with DC vaccination both increased TIL infiltration and activation in the tumor microenvironment. These findings were therapeutically relevant, with tumor-bearing mice receiving all three treatments showing a significant increase in survival over mice receiving each treatment alone. The studies outlined herein elucidated the role that TIMs play in dominantly mediating the PD-1/PD-L1 signaling mechanism to restrict TIL activation, as well as the ability to manipulate this population pharmacologically with clinically accessible agents. In conclusion, this thesis demonstrates two distinct strategies to generate and enhance an immune response against GBM. In our first strategy, we utilized the adoptive transfer of engineered T cells to selectively target an antigen whose expression we artificially induced in GBM. This technique was largely effective. However, we were interested in directly targeting antigens already expressed by GBM. To that end, we described the utility of DC vaccination in generating an immune response. Further, we delineated the inhibitory mechanisms employed by TIMs in the tumor microenvironment and developed a therapeutic adjuvant to administer with DC vaccination. We confirmed the efficacy of these treatments in a series of in vitro and in vivo animal studies, and we recapitulated these findings in our novel, ex vivo human GBM studies. Together, the studies presented in this thesis represent an innovative approach to understanding and immunotherapeutically targeting the GBM microenvironment.
Download or read book Translational Toxicology and Therapeutics written by Michael D. Waters and published by John Wiley & Sons. This book was released on 2017-11-10 with total page 716 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by leading research scientists, this book integrates current knowledge of toxicology and human health through coverage of environmental toxicants, genetic / epigenetic mechanisms, and carcinogenicity. Provides information on lifestyle choices that can reduce cancer risk Offers a systematic approach to identify mutagenic, developmental and reproductive toxicants Helps readers develop new animal models and tests to assess toxic impacts of mutation and cancer on human health Explains specific cellular and molecular targets of known toxicants operating through genetic and epigenetic mechanisms
Download or read book The Duke Glioma Handbook written by Allan H. Friedman and published by Cambridge University Press. This book was released on 2016-03-31 with total page 237 pages. Available in PDF, EPUB and Kindle. Book excerpt: Provides a summary of glioma biology, genetics and management, based on the world-leading Duke University Preston Robert Tisch Brain Tumor Center program.
Download or read book Transgenic Mouse Methods and Protocols written by Marten H. Hofker and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 382 pages. Available in PDF, EPUB and Kindle. Book excerpt: Marten Hofker and Jan van Deursen have assembled a multidisciplinary collection of readily reproducible methods for working with mice, and particularlyfor generating mouse models that will enable us to better understand gene function. Described in step-by-step detail by highly experienced investigators, these proven techniques include new methods for conditional, induced knockout, and transgenic mice, as well as for working with mice in such important research areas as immunology, cancer, and atherosclerosis. Such alternative strategies as random mutagenesis and viral gene transduction for studying gene function in the mouse are also presented.
Download or read book Immune deficient Animals written by Bernard Sordat and published by S. Karger AG (Switzerland). This book was released on 1984 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Oversight of the Office of the Intellectual Property Enforcement Coordinator written by United States. Congress. Senate. Committee on the Judiciary and published by . This book was released on 2011 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: Consists mainly of text from the book, Reconciling with the Taliban?
