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Author: Xiaozhou Fan
Publisher:
ISBN:
Category :
Languages : en
Pages : 212
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Book Description
Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) is a crucial inhibitory molecule to restrain T cell functions. CTLA-4 blockade with a monoclonal antibody (anti-CTLA-4) induces anti-tumor responses in a subset of patients and has been approved by the FDA as standard therapy for melanoma. We recently identified inducible costimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade plus ICOS engagement by tumor cell vaccines engineered to express ICOS-ligand enhanced anti-tumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong evidence to support future combinatorial approaches incorporating anti-CTLA-4 plus ICOS engagement in the clinic. We explored another strategy to enhance anti-tumor response by targeting the migration of regulatory T cells into the tumor. We proposed certain chemokines and their cognate receptors play key roles in this process. Chemokine receptors CCR4 and CCR8 are preferentially expressed by regulatory T cells in the tumor where their ligands CCL1 and CCL17 are upregulated. CCL17 was able to induce specific migration of regulatory T cells from tumor-bearing mice, and we identified a CD11b + F4/80 + Gr-1 - population in the tumor as the major source of CCL17. With an in vivo migration assay and a bone marrow chimera model, we demonstrated that CCR4 is required for the migration of regulatory T cells to the vaccine site. Lastly, we found that transfer of small numbers of naive tumor-reactive CD4 T cells into lymphopenic recipients induces substantial T cell expansion, differentiation, and regression of large established tumors without the need for in vitro manipulation. Surprisingly, CD4 T cells developed cytotoxic activity, and tumor rejection was dependent on class II-restricted recognition of tumors by tumor-reactive CD4 T cells. Furthermore, blockade of the CTLA-4 on transferred CD4 T cells resulted in greater expansion of effector T cells, diminished accumulation of regulatory T cells, and superior antitumor activity. These findings suggest a novel potential therapeutic role for cytotoxic CD4 T cells and CTLA-4 blockade in cancer immunotherapy, and the potential advantages of differentiating tumor-reactive CD4 cells in vivo.
Author: Xiaozhou Fan
Publisher:
ISBN:
Category :
Languages : en
Pages : 212
Get Book Here
Book Description
Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) is a crucial inhibitory molecule to restrain T cell functions. CTLA-4 blockade with a monoclonal antibody (anti-CTLA-4) induces anti-tumor responses in a subset of patients and has been approved by the FDA as standard therapy for melanoma. We recently identified inducible costimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade plus ICOS engagement by tumor cell vaccines engineered to express ICOS-ligand enhanced anti-tumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong evidence to support future combinatorial approaches incorporating anti-CTLA-4 plus ICOS engagement in the clinic. We explored another strategy to enhance anti-tumor response by targeting the migration of regulatory T cells into the tumor. We proposed certain chemokines and their cognate receptors play key roles in this process. Chemokine receptors CCR4 and CCR8 are preferentially expressed by regulatory T cells in the tumor where their ligands CCL1 and CCL17 are upregulated. CCL17 was able to induce specific migration of regulatory T cells from tumor-bearing mice, and we identified a CD11b + F4/80 + Gr-1 - population in the tumor as the major source of CCL17. With an in vivo migration assay and a bone marrow chimera model, we demonstrated that CCR4 is required for the migration of regulatory T cells to the vaccine site. Lastly, we found that transfer of small numbers of naive tumor-reactive CD4 T cells into lymphopenic recipients induces substantial T cell expansion, differentiation, and regression of large established tumors without the need for in vitro manipulation. Surprisingly, CD4 T cells developed cytotoxic activity, and tumor rejection was dependent on class II-restricted recognition of tumors by tumor-reactive CD4 T cells. Furthermore, blockade of the CTLA-4 on transferred CD4 T cells resulted in greater expansion of effector T cells, diminished accumulation of regulatory T cells, and superior antitumor activity. These findings suggest a novel potential therapeutic role for cytotoxic CD4 T cells and CTLA-4 blockade in cancer immunotherapy, and the potential advantages of differentiating tumor-reactive CD4 cells in vivo.
Author: Patrik Andersson
Publisher: Frontiers Media SA
ISBN: 2889631613
Category :
Languages : en
Pages : 316
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Book Description
The immune system harbors great potential for controlling and eliminating tumors. Recent developments in the field of immuno-oncology has led to unprecedented clinical benefits for a broad spectrum of solid tumors. However, immunotherapy (IT) approaches currently have several limitations including (i) low response rate; (ii) development of resistance and (iii) causing severe immune-related adverse effects (IrAEs), which underline the importance of adequate patient selection. Importantly, IT holds promising synergistic potential when combined with standard-of-care chemotherapy, radiotherapy (RT) and anti-angiogenic therapy (AAT) as part of multi-modal oncologic treatment regimes. Published data suggest that there are potential synergy between RT and AAT, which ultimately could help potentiate the response to IT. However, the complex interactions between RT and IT and/or AAT remain poorly understood. Many research questions including optimal timing, scheduling and dosing, as well as patient selection and side effects of combined therapy approaches, remain to be addressed. This Research Topic aims to give a comprehensive overview of the current field with particular emphasis on the future outlook of RT and AAT as complementary approaches to improve IT in solid tumors.
Author: Joseph D. Rosenblatt
Publisher: Springer Science & Business Media
ISBN: 1461488095
Category : Medical
Languages : en
Pages : 369
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Book Description
Recent advances in understanding of fundamental immunology have created new insights into the dynamic interactions between tumors and the immune system. This includes new understanding of T- and B-cell interaction, immune inhibitory mechanisms including the biology of T regulatory cells, myeloid suppressor cells, and dendritic cell subsets. Enhanced understanding of mechanisms underlying T-cell anergy such as arginine deprivation, immunosuppressive cytokines, defective innate and interferon response pathways, and NKG2D downregulation have all provided new insight into suppression of anti-tumor immunity and tumor evasion. In addition to emerging understanding of tumor evasion, new immune targets such as CTLA4 blockade, NK stimulatory receptors, manipulation of the antigen processing and presentation, cytokine and costimulatory responses all provide new possibilities for enhancing anti-tumor immunity even in tumors previously felt to be resistant to immune attack. Several of these strategies have already been realized in the clinic. The volume will explore evolving paradigms in antigen presentation, dendritic cell biology, the innate response and immunosuppressive mechanisms, and emerging strategies for manipulation of the immune system for therapeutic benefit that have realized success in neuroblastoma, leukemia, melanoma, lung cancer, and allogeneic transplantation. Early successes as well as failures will be highlighted to provide a snapshot of the state of clinical immunotherapy with an eye to future possibilities such as combination therapies, adoptive T-cell transfer, and the retargeting of immune cells via T-cell receptor engineering.
Author: Miyuki Azuma
Publisher: Springer Nature
ISBN: 9813297174
Category : Medical
Languages : en
Pages : 326
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Book Description
This book equips young immunologists and health professionals with a clear understanding of the fundamental concepts and roles of co-signal molecules and in addition presents the latest information on co-stimulation. The first part of the book is devoted to co-signal molecules and the regulation of T cells. Following an initial overview, subsequent chapters examine each co-signal molecule in turn and discuss the mechanisms by which co-signal molecules regulate the different types of T cell. The second part covers various clinical applications, including in autoimmune disease, neurological disorders, transplantation, graft-versus-host disease, and cancer immunotherapy. To date, co-stimulation blockade and co-inhibition blockade have shown beneficial effects and many additional clinical trials targeting co-signal molecules are ongoing. The mechanisms underlying these successful treatments are explained and the future therapeutic potential in the aforementioned diseases is evaluated. Co-signal Molecules in T Cell Activation will be a valuable reference guide to co-stimulation for basic and clinical researchers in the fields of both immunology and pharmaceutical science.
Author: Paolo A. Ascierto
Publisher: Humana Press
ISBN: 3319211676
Category : Medical
Languages : en
Pages : 315
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Book Description
This volume illustrates the salient aspects of cancer biology relevant to the successful implementation of immunotherapy. Topics include enhancement of antigen-specific immune responses by anti-cancer vaccines, modulation of the function of T cells within the tumor microenvironment, and the effects of genetic, epigenetic, developmental, and environmental determinants on T cell function. Other topics covered include the ex vivo expansion of T or other immune cells and their genetic modification or reprogramming to increase their ability to survive and expand when adoptively transferred back to the patients. Specific attention is devoted to the genetic manipulation of T cells through the introduction of re-directed T cell receptors, chimeric antibody receptors, and other genetic manipulation aimed at improving their effectiveness as anti-cancer agents. Furthermore, the revolutionary role of checkpoint inhibitors and their potential in combination with other immunotherapeutic approaches or with standard chemo and radiation therapy are extensively discussed.
Author: Hans J Stauss
Publisher: CRC Press
ISBN: 1134433336
Category : Medical
Languages : en
Pages : 355
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Book Description
Recent progress in fundamental tumor immunology has led to immunotherapy trials in patients with solid tumors and hematological malignancies. In the past, immunotherapy approaches were primarily based on enhancement of tumor immunity with cytokines and adjuvant therapy, without knowledge of relevant tumor antigens. The discovery of tumor antigens c
Author: James H. Finke
Publisher: Springer Science & Business Media
ISBN: 1592597432
Category : Medical
Languages : en
Pages : 392
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Book Description
Leading investigators and clinicians detail the different mechanisms used by tumors to escape and impair the immune system and then spell out possible clinical strategies to prevent or reverse tumor-induced immune dysfunction. The authors review the mechanisms of immune dysfunction and evasion mechanisms in histologically diverse human tumors, focusing on tumor-induced molecular defects in T cells and antigen-presenting cells (dendritic cells and tumors), that may serve as biomarkers for patient prognosis. They discuss the means by which these immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques are outlined with the capacity to monitor the strength and quality of patients' immune responses using immunocytometry, MHC-peptide tetramers combined with apoptosis assay, ELISPOT assay, and detection of MHC-TAA peptide complexes on tumor cells.
Author: Daniel W. Lee
Publisher: Elsevier Health Sciences
ISBN: 0323755976
Category : Medical
Languages : en
Pages : 246
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Book Description
From patient referral to post-therapy management, Chimeric Antigen Receptor (CAR) T-Cell Therapies for Cancer: A Practical Guide presents a comprehensive view of CAR modified T-cells in a concise and practical format. Providing authoritative guidance on the implementation and management of CAR T-cell therapy from Drs. Daniel W. Lee and Nirali N. Shah, this clinical resource keeps you up to date on the latest developments in this rapidly evolving area. - Covers all clinical aspects, including patient referral, toxicities management, comorbidities, bridging therapy, post-CAR monitoring, and multidisciplinary approaches to supportive care. - Includes key topics on associated toxicities such as predictive biomarkers, infections, and multidisciplinary approaches to supportive care. - Presents current knowledge on FDA approved CAR T-cell products as well as developments on the horizon. - Editors and authors represent leading investigators in academia and worldwide pioneers of CAR therapy.
Author: Emmanuel Donnadieu
Publisher: Springer
ISBN: 3319422235
Category : Medical
Languages : en
Pages : 202
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Book Description
This volume focuses on recent advances in understanding T cells as key players in antitumor immune responses, and as a result T cell-based immunotherapy is starting to transform the treatment of advanced cancers. However, despite recent successes, many patients with cancer fail to respond to these treatments. Defective migration of T cells into and within tumors is considered as an important resistance mechanism to cancer immunotherapy.The volume includes three sections. The first section covers general knowledge about T cell trafficking during a normal immune response but also during tumor development. The second section provides an in-depth description of the different obstacles that prevent T cells from migrating and contacting tumor cells. The third section explores therapeutic strategies to improve trafficking of T cells into tumors and, thus, to enhance the effectiveness of cancer immunotherapy.
Author:
Publisher: Academic Press
ISBN: 0128188758
Category : Science
Languages : en
Pages : 346
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Book Description
Tumor Immunology and Immunotherapy Integrated Methods - Part A, Volume 635 in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. Specific chapters to this release include Deconvolution of the immunological contexture of mouse tumors with multiplexed immunohistochemistry, High-dimensional multiplexed immunohistochemical characterization of immune contexture in human cancers, Multiplex assay by IHC for melanoma tumor microenvironment evaluation, Characterization of the tumor immune microenvironment by multispectral image analysis of multiplex immunofluorescence images, Phenotyping of immune cells in situ using multispectral imaging quantification, and much more. - Authored by leaders in the field of enzymology - Provides a comprehensiveness level of discussion on the field - Presents a highly specialized group of topics that delve deep into new updates and future prospects
