Tumor Microenvironment Regulation of Tumor Expansion

Tumor Microenvironment Regulation of Tumor Expansion
Author: Domenico Ribatti
Publsiher: Academic Press
Total Pages: 172
Release: 2021-04-04
ISBN 10: 0128228040
ISBN 13: 9780128228043
Language: EN, FR, DE, ES & NL

Tumor Microenvironment Regulation of Tumor Expansion Book Review:

Tumor Microenvironment Regulation of Tumor Expansion is a practical guide to understand and perform research on tumor microenvironments, and to support related clinical decisions. Tumor progression is linked to an imbalance between positive and negative regulators, and mainly depends on the release of specific growth factors by inflammatory or neoplastic cells. Inflammatory infiltrate contributes to tumor progression and the metastatic process, and there are many reports of associations between tumor inflammatory infiltrate, progression, and prognosis. Understanding different contexts of organs is a key factor in improving treatment outcome, especially in new therapeutic treatments targeting components of the tumor microenvironment. This book is a valuable resource for cancer researchers, clinicians, graduate students, and scientists in many biomedical fields who are interested in the complex relationship between the tumor microenvironment and its context in specific organs. Provides a holistic approach to understanding the crucial role of the tumor microenvironment in tumor progression Encompasses the basic knowledge necessary to understand and undertake further studies related to tumor microenvironments Discusses new therapeutic approaches developed to control tumor progression by targeting different components of the tumor microenvironment

General Principles of Tumor Immunotherapy

General Principles of Tumor Immunotherapy
Author: Howard L. Kaufman,Jedd D. Wolchok
Publsiher: Springer Science & Business Media
Total Pages: 503
Release: 2007-10-12
ISBN 10: 1402060874
ISBN 13: 9781402060878
Language: EN, FR, DE, ES & NL

General Principles of Tumor Immunotherapy Book Review:

This book brings together the world’s leading authorities on tumor immunology. This book describes the basic immunology principles that form the foundation of understanding how the immune system recognizes and rejects tumor cells. The role of the innate and adaptive immune responses is discussed and the implications of these responses for the design of clinical strategies to combat cancer are illustrated.

The Cancer Stem Cell Niche

The Cancer Stem Cell Niche
Author: Susie Prof. Nilsson
Publsiher: Academic Press
Total Pages: 246
Release: 2021-01-23
ISBN 10: 0323853269
ISBN 13: 9780323853262
Language: EN, FR, DE, ES & NL

The Cancer Stem Cell Niche Book Review:

The Cancer Stem Cell Niche, Volume Five in the Advances in Stem Cells and their Niches series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics, including Acute lymphoblastic leukemia and the bone marrow microenvironment, Stem cell niches in bone and their roles in cancer metastasis, The role of vasculature in cancer stem cell niches, The lung cancer stem cell niche, The prostate cancer stem cell niche: Genetic drivers and therapeutic approaches, Impact of prostate cancer stem cell niches on prostate cancer tumorigenesis and progression, The testicular cancer stem cell niche. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Stem Cells and their Niches series Includes the latest information on the Cancer Stem Cell Niche

Tumor Microenvironment

Tumor Microenvironment
Author: Alexander Birbrair
Publsiher: Springer Nature
Total Pages: 146
Release: 2020-02-08
ISBN 10: 3030357236
ISBN 13: 9783030357238
Language: EN, FR, DE, ES & NL

Tumor Microenvironment Book Review:

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.

Pleiotropic Action of Selenium in the Prevention and Treatment of Cancer and Related Diseases

Pleiotropic Action of Selenium in the Prevention and Treatment of Cancer  and Related Diseases
Author: Youcef M. Rustum
Publsiher: MDPI
Total Pages: 166
Release: 2019-03-26
ISBN 10: 303897692X
ISBN 13: 9783038976929
Language: EN, FR, DE, ES & NL

Pleiotropic Action of Selenium in the Prevention and Treatment of Cancer and Related Diseases Book Review:

Gene cloning and sequence has provided the opportunity to identify and characterize the functional role of biomarkers expressed in and on tumor cells and the surrounding microenvironment. Molecular and immunologic heterogeneity of cells in the tumor microenvironment contributes to instability, enhanced angiogenesis, and drug resistance of the tumor cell. Since tumor cells are the ultimate therapeutic targets for drugs and therapy development, the tumor microenvironment that regulates the growth and the delivery of effective drug concentrations to tumor cells is the gatekeeper. Thus, to have a significant impact on the overall survival and cure of patients with advanced cancer, the stabilization of the tumor microenvironment should be the initial treatment, followed by treatment that targets and kills tumor cells. Antiangeogenic therapies hold considerable promise in the treatment of a subset of cancer patients and are reported to have a significant impact on the stabilization of the tumor microenvironment. More recently, selenium-containing molecules, such as se-metylselenocysteine, seleno-L-methionine, and selenized yeast, among others, have been shown to target and modulate biomarkers associated with tumor cells and the tumor microenvironment. The effects are selenium type-, dose-, and schedule-dependent. The pleiotropic actions of selenium are necessary for tumor cell sensitization, and synergy with mechanism-based combinations. This Special Issue is devoted to highlighting evidence for the potential role of specific types, doses, and schedules of selenium alone and in combination with mechanism-based biologic and cytotoxic therapies for the prevention and treatment of cancer and related diseases. The collection of contributions should provide a comprehensive overview of the pharmacology, metabolism, and delineation of the pleiotropic action of different types of selenium molecules, relevant to the use of selenium as a potential modulator of the therapeutic efficacy and toxicity of biologic and cytotoxic therapies for cancer and related diseases. The pleiotropic action of specific types of selenium, doses, and schedule, as a selective and efficacious modulator of genetic, immunologic, and epigenetic biomarkers, should stimulate expanded preclinical research that could ultimately impact the development of new and novel approaches for the treatment of cancer.

Effect of Cyclosporin A on the Tumor Microenvironment

Effect of Cyclosporin A on the Tumor Microenvironment
Author: Yao Zhou
Publsiher: Unknown
Total Pages: 298
Release: 2014
ISBN 10: 1928374650XXX
ISBN 13: OCLC:909959971
Language: EN, FR, DE, ES & NL

Effect of Cyclosporin A on the Tumor Microenvironment Book Review:

Tumor angiogenesis is a hallmark of cancer, and plays a critical role in tumor growth, expansion, and metastasis. Both physiological and pathological angiogenesis is assumed to be regulated by the balance between pro and anti-angiogenic factors. One of the best characterized and most potent pro-angiogenic regulators is vascular endothelial growth factor, or VEGF. Calcineurin signaling is an important mediator of VEGF signaling in endothelial cells. Negative regulation of calcineurin by increased expression of its endogenous inhibitor, Down Syndrome Candidate Region-1 (DSCR1), suppresses tumor growth and angiogenesis. However, a potent pharmacological calcineurin inhibitor, the commonly used immunosuppressant cyclosporin A (CsA), significantly increases the incidence of cancer in organ transplant recipients. The mechanism by which CsA promotes cancer in this patient population is not well understood and despite the significance of calcineurin signaling in endothelial cells, the consequences of CsA on tumor angiogenesis has not been investigated. Using an in vivo model of skin carcinogenesis, we show that long-term CsA treatment promotes tumor growth and angiogenesis. Further our data indicate that treatment of endothelial cells in vitro with CsA increases proliferation and migration, in a calcineurin-independent manner. Our studies reveal that CsA-induced endothelial cell activation was due to the interaction of CsA with cyclophilin D located on the mitochondrial inner membrane. CsA treatment in endothelial cells increased mitochondrial membrane potential and mitochondrial reactive oxygen species production, and was associated with sustained mitogen-activated protein kinase (MAPK) activity. Co-treatment with antioxidants significantly abrogated CsA-induced endothelial cell activation. Furthermore, mice treated with antioxidants were protected against CsA-mediated tumor progression. Taken together, these findings show that CsA functions independent of calcineurin to potentiate tumor growth by promoting tumor angiogenesis via mitochondrial reactive oxygen species production. This work identifies a previously undescribed mechanism underlying a significantly adverse off-target effect of CsA and suggests that co-treatment with antioxidants may inhibit the tumor promoting effects of CsA.

Role of ZEB1 in Macrophages During Homeostasis Inflammation and Cancer

Role of ZEB1 in Macrophages During Homeostasis  Inflammation and Cancer
Author: Marlies Cortés Hinojosa
Publsiher: Unknown
Total Pages: 156
Release: 2018
ISBN 10: 1928374650XXX
ISBN 13: OCLC:1055884986
Language: EN, FR, DE, ES & NL

Role of ZEB1 in Macrophages During Homeostasis Inflammation and Cancer Book Review:

ZEB1 is a transcription factor whose expression in cancer cells promotes tumor initiation and progression. In this study, we for the first time characterized Zeb1 and study its function in macrophages under either homeostasis or activation conditions as well as in a murine cancer model. We found that macrophages deficient for Zeb1 showed aberrant characteristics in phenotype and functions, under physiological and pathological conditions. Here we clarified a functional role of Zeb1 on macrophages playing a role in macrophage phagocytosis, migration and inflammation as well as in tumor progression in a non-cell-autonomous manner modulating the tumor microenviroment. In fact the evidence presented indicates that the downregulation of Zeb1 in macrophages is associated with the inhibition of TAM characteristics and inhibition of tumor progression. ZEB1 plays important roles during embryogenesis and deletion of both alleles of Zeb1 in mice results in embryonic lethality. ZEB1 represses key genes involved in the terminal differentiation of multiple tissues, including inter alia epithelial cells, pituitary gland, skeletal and smooth muscle, cartilage, and bone. Although ZEB1 is expressed in lymphoid cells where it represses pivotal hematopoietic transcription factors, there was no evidence for a role of ZEB1 in the regulation of lymphoid or myeloid differentiation. We showed here that downregulation of Zeb1 in bone marrow precursors promoted their differentiation towards macrophages. These data further support a model, best characterized in epithelial tissues and skeletal muscle, where ZEB1 expression needs to decline for early precursors to terminally differentiate. ZEB1 has been extensively characterized in cancer cells where it promotes their stemness, survival and invasiveness. However, its role in the tumor microenvironment remained to be elucidated. Among cancer cells, ZEB1 is not expressed across the entire tumor mass but is rather restricted to a subpopulation of stem-like malignant cells at the invasive front, actually, at the interface where cancer cells and TAMs interact. Although ZEB1 expression among stromal cells has been noted, the identity of the cell types expressing ZEB1 has not been established. This study showed that ZEB1 is also expressed in TAMs and that ZEB1 not only bilaterally regulates the crosstalk between cancer cells and TAMs but that this crosstalk regulates ZEB1 expression itself. Thus, Zeb1 was upregulated in macrophages that have interacted with cancer cells as well as in cancer cells that have interacted with wild-type TAMs. The tumor-promoting role of ZEB1 is therefore supported by a positive feedback of its expression between malignant cells and TAMs. We found that Zeb1 is restricted to the F4/80low macrophage/TAM subpopulation—previously known to display stronger pro-tumor and pro-angiogenic functions—whose share is expanded by ZEB1. Soluble factors produced by the tumor—e.g., CSF1 and CCL2—attract F4/80low CCR2+ monocytes into their microenvironment where they are activated into TAMs. Inhibition of the CCL2–CCR2 axis blocks monocyte recruitment into the tumor stroma and inhibits tumor growth. We found that Zeb1 promotes monocyte migration both in response to chemotactic stimuli (CSF1 and CCL2) and in the context of cancer. Zeb1-deficient TAMs expressed lower levels of Ccr2 and were unable to induce Ccl2 in ID8 cells. At the same time, the maximum effect of ZEB1 as a biomarker of poorer prognosis in ovarian cancer patients depended on high levels of CCL2. These data establish Zeb1 as an important inducer of the pro-tumor and pro-metastatic CCR2-07P9-CCL2 loop between tumor cells and TAMs. It is important to note that this CCR2-07P9-CCL2 loop was inhibited by just a partial downregulation of Zeb1 in TAMs. Data here showed that the pro-tumor role of ZEB1 in TAMs also depends on a similarly narrow threshold of expression. Zeb1 (+/-) macrophages still express about half of the Zeb1 mRNA levels of wild-type macrophages, but this downregulation was enough to render Zeb1 (+/-) TAMs unable to promote tumor growth when transplanted into tumor-bearing mice as wild-type macrophages did. As in the case of ZEB1 expression in cancer cells, to the best of our knowledge, this is the first example of a heterozygous gene deletion being sufficient to block the tumor-promoting role of TAMs. Expression of ZEB1 in cancer cells has been associated to increased chemotherapy resistance. In parallel, we found here that expression of ZEB1 in TAMs also increased the cancer cell resistance to chemotherapy. In that line, we showed that Zeb1 in TAMs increased the expression of Il10, Mmp9 and Il1b—that have a suppressor effect on chemotherapy—and of the drug efflux transporter Mdr1. The dual role of ZEB1 promoting tumor progression in cancer cells and in TAMs—albeit through different mechanisms—has translational implications. Targeting ZEB1 in cancer cells is being considered in ongoing clinical trials but data here suggest that improving chemotherapy response would also require the downregulation of ZEB1 in TAMs. The fact that a partial downregulation of Zeb1 in TAMs was sufficient to abolish TAMs' tumor-promoting function is highly relevant for therapy approaches aiming at blocking ZEB1 expression and/or function. These results establish a new role for ZEB1 promoting tumor progression through its expression in TAMs, thus setting ZEB1 expression as a relevant target in cancer therapy.

Mesenchymal Stromal Cells as Tumor Stromal Modulators

Mesenchymal Stromal Cells as Tumor Stromal Modulators
Author: Marcela Bolontrade,Mariana García
Publsiher: Academic Press
Total Pages: 642
Release: 2016-10-24
ISBN 10: 0128031034
ISBN 13: 9780128031032
Language: EN, FR, DE, ES & NL

Mesenchymal Stromal Cells as Tumor Stromal Modulators Book Review:

Mesenchymal stromal/ stem cells (MSCs) represent a heterogeneous cell population with immunomodulating, tissue repairing, differentiating, migratory and angiogenic abilities, making them important tools for clinical and translational research. An understanding of the role of MSCs in modulating tumor growth provides a glimpse into their role in non-pathological tissue remodeling and potential regenerative tissue therapies. Mesenchymal Stromal Cells as Tumor Stromal Modulators is a comprehensive source for the understanding of the role of MSCs as ubiquitous connective tissue cell components, which may have both direct and indirect effects on the tumor microenvironment and potential for regenerative therapeutics for various diseases. Using cancer as a model disease, this book explores the transformative role MSCs play in the recruitment of disease cells, cell repair and immunological defenses. Explores the biology of mesenchymal stromal cells (MSCs) and tissue related function Discusses the bidirectional communication between tumor stroma and MSCs derived from bone marrow, from adipose tissue and from other tissue types Provides in-depth analysis of the effects of MSCs on key processes that regulate disease progression, such as angiogenesis, metastatic potential, invasion, proliferation, tumor immune privileges

Immune Suppression and Inflammation in the Progression of Breast Cancer

Immune Suppression and Inflammation in the Progression of Breast Cancer
Author: Anonim
Publsiher: Unknown
Total Pages: 130
Release: 2008
ISBN 10: 1928374650XXX
ISBN 13: OCLC:318690452
Language: EN, FR, DE, ES & NL

Immune Suppression and Inflammation in the Progression of Breast Cancer Book Review:

Epidemiological and experimental evidence supports the concept that chronic inflammation promotes and enhances cancerous growth through several key mechanisms, although these processes are not well understood. Several important mechanisms by which inflammation may initiate and support malignant progression have been previously described, such as the induction of DNA damage, the promotion of angiogenesis and new vasculature, and the production of growth and survival factors. The purpose of this study is to identify a novel mechanism by which chronic inflammation may support and advance tumor progression, through the induction and expansion of immune suppressive mechanisms. We demonstrate that chronic inflammation induces tumor-associated immune-suppression, by enhancing the accumulation of a population of immature myeloid-derived suppressor cells (MDSC), which down regulate and inhibit anti-tumor immunity, allowing for the proliferation and outgrowth of transformed cells. To study the association between inflammation and immune suppression in the context of tumor progression, the 4T1 mammary carcinoma cell line engineered to secrete the pro-inflammatory cytokine interleukin 1 beta (4T1/IL-1beta) was used to create an inflammatory tumor microenvironment. Additionally, IL-1 receptor (IL-1R)-deficient mice, which have a reduced potential for inflammation, and IL-1 receptor antagonist (IL-1Ralpha)-deficient mice, which have an increased potential for inflammation, were used to modulate the inflammatory milieu, and the effects of inflammation on primary and metastatic tumor progression and immune suppression were examined. The presence of IL-1beta in the tumor microenvironment promotes the induction and expansion of a more potent suppressive population of MDSC, thereby enhancing tumor growth and reducing survival.

Tumor Microenvironment

Tumor Microenvironment
Author: Alexander Birbrair
Publsiher: Springer Nature
Total Pages: 160
Release: 2020-02-06
ISBN 10: 3030357279
ISBN 13: 9783030357276
Language: EN, FR, DE, ES & NL

Tumor Microenvironment Book Review:

This volume discusses recent research advances in cancer biology, focusing on the role of the tumor microenvironment. Taken alongside its companion volumes, Tumor Microenvironment: Recent Advances covers the latest research on various aspects of the tumor microenvironment, as well as future directions. Useful for introducing the newer generation of researchers to the history of how scientists studied the tumor microenvironment as well as how this knowledge is currently applied for cancer treatments, it will be essential reading for advanced cell biology and cancer biology students, as well as researchers seeking an update on research on the tumor microenvironment.

Tumor Microenvironment and Resistance to Current Therapies

Tumor Microenvironment and Resistance to Current Therapies
Author: Ahmed Lasfar,Andrew Zloza,Karine A. Cohen-Solal,Murugabaskar Balan
Publsiher: Frontiers Media SA
Total Pages: 135
Release: 2020-01-27
ISBN 10: 2889632830
ISBN 13: 9782889632831
Language: EN, FR, DE, ES & NL

Tumor Microenvironment and Resistance to Current Therapies Book Review:

Molecular Strategies Aimed to Boost NK Cell based Immunotherapy of Cancer

Molecular Strategies Aimed to Boost NK Cell based Immunotherapy of Cancer
Author: Loredana Cifaldi,Daniel Olive,James Di Santo
Publsiher: Frontiers Media SA
Total Pages: 135
Release: 2020-07-31
ISBN 10: 2889638766
ISBN 13: 9782889638765
Language: EN, FR, DE, ES & NL

Molecular Strategies Aimed to Boost NK Cell based Immunotherapy of Cancer Book Review:

In this Research Topic, we would like to honor the memory of Prof. Vito Pistoia and pay tribute to his scientific contributions to the field of Cancer Immunity and Immunotherapy. Topic Editor Daniel Olive is the co-founder and shareholder of company Imcheck Therapeutics. All other topic editors declare no competing interests with regards to the Research Topic subject.

The regulation of angiogenesis by tissue cell macrophage interactions

The regulation of angiogenesis by tissue cell macrophage interactions
Author: Michal Amit Rahat,Bernhard Hemmerlein,Vijaya Iragavarapu-Charyulu
Publsiher: Frontiers E-books
Total Pages: 135
Release: 2014-11-03
ISBN 10: 2889193179
ISBN 13: 9782889193172
Language: EN, FR, DE, ES & NL

The regulation of angiogenesis by tissue cell macrophage interactions Book Review:

Angiogenesis is the physiological process where new blood vessels grow from existing ones, in order to replenish tissues suffering from inadequate blood supply. Perhaps the most studied angiogenic process occurs in solid tumors whose growing mass and expanding cells create a constant demand for additional supply of oxygen and nutrients for survival. However, other physiological and clinical conditions, such as wound healing, ischemic events, autoimmune and age-related diseases also involve angiogenesis. Angiogenesis is a well-structured process that begins when oxygen and nutrients are depleted, leading to the release of chemokines and growth factors that attract immune cells, particularly macrophages and endothelial cells to the site. Macrophages that are recruited to the site, as well as tissue cells and endothelial cells, secrete pro-angiogenic mediators that affect endothelial cells and promote angiogenesis. These mediators include growth factors such as vascular endothelial cell growth factor (VEGF), matrix metalloproteinases (MMPs), as well as low levels of mediators that are usually seen as pro-inflammatory but are pro-angiogenic when secreted in low levels (e.g. nitric oxide (NO) and TNFa). Thus, macrophages play a major role in angiogenesis. Macrophages exhibit high plasticity and are capable of shifting between different activation modes and functions according to their changing microenvironment. Small differences in the composition of activating factors (e.g. TLR ligands such as LPS, anti-inflammatory cytokines, ECM molecules) in the microenvironment may differently activate macrophages to yield classically activated macrophages (or M1 macrophages) that can kill pathogen and tumor cells, alternatively activated macrophages (or M2 macrophages) that secrete antiinflammatory cytokines, resolution macrophages (rM?) that are involved in the resolution of inflammation, or regulatory macrophages (e.g. Myeloid-Derived Suppressor Cells - MDSCs) that control the function of other immune cells. In fact, macrophages may be activated in a spectrum of subsets that may differently contribute to angiogenesis, and in particular non-classically activated macrophages such as tumor-associated macrophages (TAMs) and Tie2-expressing monocytes (TEMs) can secrete high amounts of pro-angiogenic factors (e.g. VEGF, MMPs) or low levels of pro-inflammatory mediators (e.g. NO or TNFa) resulting in pro-angiogenic effects. Although the importance of macrophages as major contributors and regulators of the angiogenic process is well documented, less is known about the interactions between macrophages and other cell types (e.g. tumor cells, normal epithelial cells, endothelial cells) that regulate angiogenesis. We still have only limited understanding which proteins or complexes mediate these interactions and whether they require cell-cell contact (e.g. through integrins) or soluble factors (e.g. the EGF-CSF-1 loop), which signaling pathways are triggered in each of the two corresponding cell types, and how this leads to secretion of pro- or antiangiogenic factors in the microenvironment. The regulation of such interactions and through them of angiogenesis, whether through post-translational modifications of proteins or via the involvement of microRNA, is still unclear. The goal of this Research Topic is to highlight these interactions and their regulation in the context of both physiological and pathological conditions.

Expansion of Highly Cytotoxic Human Natural Killer Cells by Osteoclast for Cancer Immunotherapy

Expansion of Highly Cytotoxic Human Natural Killer Cells by Osteoclast for Cancer Immunotherapy
Author: So-Hyun Park
Publsiher: Unknown
Total Pages: 105
Release: 2015
ISBN 10: 1928374650XXX
ISBN 13: OCLC:926076523
Language: EN, FR, DE, ES & NL

Expansion of Highly Cytotoxic Human Natural Killer Cells by Osteoclast for Cancer Immunotherapy Book Review:

Natural Killer (NK) cells have a crucial role in immune surveillance against a variety of infectious microorganisms and tumors. NK cells are known to mediate direct cytotoxicity as well as antibody dependent cellular cytotoxicity (ADCC) against a variety of tumor cells. Also, they are known to regulate the functions of other cells by producing key cytokines and chemokines. In the tumor microenvironment, cytotoxic function of NK cells is suppressed by a number of distinct effectors and their secreted factors. It has been shown that many cancer patients have decreased peripheral blood NK cell function, so NK cell-based immunotherapy has been used as a treatment in order to enhance NK cell function. However, limited availability of NK cells and ability to expand has restricted development of NK cell immunotherapy. Overcoming NK cell tolerance against tumors by developing new ways of activating endogenous NK cells that increase the expression of ligands for activating NK cell receptors or that render them more sensitive to NK cell mediated killing is crucial. In this study, we found the novel way to expand NK cells and the functionality of NK cells generated under this condition demonstrated enhanced expression of activating NK receptors. Also, significant cytotoxic killing potential after culture was discovered as well as augmented cytokine secretion. Therefore, these expanded NK cells are highly functional in comparison to primary NK cells. Through the help of cytokines, sAJ2 bacteria and osteoclast, NK cells can be expanded and activated in vitro and furthermore, these expanded NK cells can be used to target tumors in vivo. Expanded NK cells can be used in combination with other treatment modalities, potentially leading to synergistic antitumor activities.

Tumor Microenvironment and Cellular Stress

Tumor Microenvironment and Cellular Stress
Author: Constantinos Koumenis,Ester Hammond,Amato Giaccia
Publsiher: Springer Science & Business Media
Total Pages: 290
Release: 2013-11-23
ISBN 10: 146145915X
ISBN 13: 9781461459156
Language: EN, FR, DE, ES & NL

Tumor Microenvironment and Cellular Stress Book Review:

The collection of chapters in this proceeding volume reflects the latest research presented at the Aegean meeting on Tumor Microenvironment and Cellular Stress held in Crete in Fall of 2012. The book provides critical insight to how the tumor microenvironment affects tumor metabolism, cell stemness, cell viability, genomic instability and more. Additional topics include identifying common pathways that are potential candidates for therapeutic intervention, which will stimulate collaboration between groups that are more focused on elucidation of biochemical aspects of stress biology and groups that study the pathophysiological aspects of stress pathways or engaged in drug discovery.

Novel Immunotherapeutic Approaches to the Treatment of Cancer

Novel Immunotherapeutic Approaches to the Treatment of Cancer
Author: Paul D. Rennert
Publsiher: Springer
Total Pages: 276
Release: 2016-05-30
ISBN 10: 3319298275
ISBN 13: 9783319298276
Language: EN, FR, DE, ES & NL

Novel Immunotherapeutic Approaches to the Treatment of Cancer Book Review:

Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered. The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.

Regulatory Mechanism of Myeloid Derived Suppressor Cell Activity

Regulatory Mechanism of Myeloid Derived Suppressor Cell Activity
Author: Cesar Alexander Corzo
Publsiher: Unknown
Total Pages: 202
Release: 2010
ISBN 10: 1928374650XXX
ISBN 13: OCLC:681787366
Language: EN, FR, DE, ES & NL

Regulatory Mechanism of Myeloid Derived Suppressor Cell Activity Book Review:

ABSTRACT: Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network that develops during cancer. MDSC down-regulate immune surveillance and antitumor immunity and facilitate tumor growth. The ability of MDSC to suppress T cell responses has been documented; however the mechanisms regulating this suppression remain to be understood. This work proposes a biological dichotomy of MDSC regulated by the tumor microenvironment. In peripheral lymphoid organs MDSC cause T-cell non-responsiveness that is antigen-specific. These MDSC have increased expression of NOX2, enabling them to produce large amounts of reactive oxygen species. Since the transcription factor STAT3 is substantially activated in MDSC, its potential role in upregulation of NOX2 expression was investigated. Over-expression of a constitutively active form of STAT3 increases expression of NOX2 subunits, whereas attenuation of STAT3 activity leads to decreased expression of NOX2. The significance of NOX2 in ROS generation is demonstrated in mice devoid of NOX2 function; NOX2-deficient MDSC are unable to inhibit antigen-induced activation of T cells. In contrast, MDSC within the tumor microenvironment have a diminished potential to generate ROS but acquire expression of arginase and inducible nitric oxide synthase, enzymes implicated in T cell non-responsiveness. Upregulation of these enzymes results in MDSC ability to inhibit lymphocyte response in absence of antigen presentation. The tumor microenvironment also promotes the differentiation of MDSC to tumor associated macrophages. Hypoxia is an exclusive feature to the tumor microenvironment and we investigated its involvement in the properties of MDSC at the tumor site. Exposure of spleen MDSC to hypoxia converts MDSC to non-specific suppressors and induces a preferential differentiation to macrophages. Stabilization of HIF-1alpha, a transcription factor activated by hypoxia, induces similar changes in MDCS as hypoxic exposure. Finally, ablation of HIF-1alpha prevents MDSC from acquiring factors that enable the suppression of T cells in absence of antigen. These findings help to expand our understanding of the biology of MDSC and suggest a regulatory pathway of myeloid cell function exclusive to the tumor microenvironment. They may also open new opportunities for therapeutic regulation as we now should take into consideration how systemic location affects the function of MDSC.

Tumor Induced Immune Suppression

Tumor Induced Immune Suppression
Author: Dmitry I. Gabrilovich,Arthur Andrew Hurwitz
Publsiher: Springer Science & Business Media
Total Pages: 464
Release: 2014-02-10
ISBN 10: 1489980563
ISBN 13: 9781489980564
Language: EN, FR, DE, ES & NL

Tumor Induced Immune Suppression Book Review:

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.

Reuglation of T Helper 17 by Bacteria

Reuglation of T Helper 17 by Bacteria
Author: Ying-Ju Cecilia Sung,宋穎如
Publsiher: Open Dissertation Press
Total Pages: 135
Release: 2017-01-27
ISBN 10: 9781361369074
ISBN 13: 1361369078
Language: EN, FR, DE, ES & NL

Reuglation of T Helper 17 by Bacteria Book Review:

This dissertation, "Reuglation of T Helper 17 by Bacteria: an Approach for the Treatment of Hepatocellular Carcinoma" by Ying-ju, Cecilia, Sung, 宋穎如, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related deaths in the world. It is a disease with poor prognosis with unsatisfactory long-term survival of patients, and thus new strategies to control this disease are warranted. T helper (Th) 17 cells and IL-17 have recently been detected with increased frequency in a number of tumors including HCC. Its role in tumor remains controversial but its presence in HCC has been linked to disease progression, possibly involving angiogenesis. Th17 cells could be homed to inflammatory sites such as tumor microenvironment via CCR6/CCL20 axis and expand locally, and studies from other inflammatory diseases such as autoimmune disease has shown that the gut is the potential source of Th17, where its induction is affected by signals from gut microbiota. Yet this link is not yet shown in extra-intestinal tumors. Probiotics are living microorganisms, which when administered in adequate amounts confer a health benefit on the host. They have been reported to relieve chronic inflammatory diseases in animal and in human intervention studies. It is believed that probiotics regulate signals to gut antigen-presenting cells, which act as the pivot in modulating the systemic immune responses and inactivated bacteria also exhibited immunomodulatory effects in this regard. Accordingly, it was hypothesized that oral feeding of probiotics to HCCbearing animals may affect Th17 polarization and distribution and thereby modulate tumor microenvironment, which may have beneficial effect in tumor development, possibly via affecting angiogenesis. To address this hypothesis, wild-type C57BL/6 mice were fed with different heat-inactivated or viable probiotics- Lactobacillus rhamnosus GG (LGG), Escherichia coli Nissle 1917 (EcN), VSL#3 or mixture of probiotics - Prohep (heat-inactivated LGG, heatinactivated VSL#3 and viable EcN) either one week in advance or at the time of subcutaneous tumor inoculation. Probiotic feeding had improved survival in tumor-bearing mice, slowed down tumor growth and reduced tumor burden when monitored for 38 days. Probiotics showed better efficacy when feeding was given in advance. The anti-tumor effect was related to reduced angiogenesis and reduced IL-17 serum and gene expression within tumor. The mechanistic link between IL-17 modulation and tumor development was further studied in animals by IL-17 neutralization. The anti-tumor efficacy of probiotics, in relation to tumor growth and angiogenesis, was lost after IL-17 neutralization, which was linked to recruitment of myeloid suppressor cells. Since cells from both adaptive and innate immune systems could secrete IL-17, the source of IL-17 production was then identified, and found that Th17 was the major IL-17 secretor being modulated by probiotic feeding. Reduced homing of Th17 to tumor via circulation, with a tendency being recruited from gut was observed. Probiotics-mediated Th17 cell modulation in the gut by inducing the skewing of IL-10 secreting type1 regulatory T cells via dendritic cells may link to limited IL-17 mediated angiogenesis in the tumor microenvironment. With better understanding of the immunomodulation properties of probiotics, prophylactic or therapeutic efficacy in management of other inflammation-associated cancer can be availed. DOI: 10.5353/th_b5387

Development of a Lymphatic Organotypic Microfluidic Model to Study the Influence of the Tumor Microenvironment in Lymphatic Vessel Function

Development of a Lymphatic Organotypic Microfluidic Model to Study the Influence of the Tumor Microenvironment in Lymphatic Vessel Function
Author: Karina Marie Lugo-Cintron
Publsiher: Unknown
Total Pages: 194
Release: 2020
ISBN 10: 1928374650XXX
ISBN 13: OCLC:1141858875
Language: EN, FR, DE, ES & NL

Development of a Lymphatic Organotypic Microfluidic Model to Study the Influence of the Tumor Microenvironment in Lymphatic Vessel Function Book Review:

Metastasis is the leading cause of death in cancer patients and, once cancer cells spread from the primary tumor, treatment becomes challenging. A key step during cancer metastasis is cancer cell intravasation (i.e., entry of cancer cells into the blood or lymphatic vasculature) that results in tumor cell dissemination to distant organs. Certain cancers (e.g., breast and head and neck), preferentially spread out of the primary tumor using the lymphatic vasculature, a process that is regulated by the interactions between cancer cells, the lymphatic vasculature and the surrounding tumor microenvironment (TME). Despite the identification of mechanisms that cancer cells use to intravasate into lymphatic vessels, lymphatic metastasis remains a problem. In this regard, recent studies have highlighted the critical role the TME plays in lymphatic metastasis and, recently emerged as a potential new target to inhibit tumor growth and metastasis. Therefore, there is a need to better understand how components of the TME influence lymphatic vessels to identify new therapeutic targets that prevent metastasis. To study lymphatics, traditional cell culture approaches (e.g., petri dishes) have been used, however, these approaches lack the complexity of the biological structures. Hence, to understand the influence of different TME components in lymphatics, a microfluidic in vitro model that can recapitulate the physiological conditions found in vivo would be a beneficial tool to advance cancer research. Thereby, this Ph.D. thesis presents the development of an organotypic lymphatic vessel model to study the influence of different tumor microenvironment components in lymphatic vessel remodeling. Altogether, this dissertation highlights the first microfluidic organotypic lymphatic model that enabled the examination of TME-lymphatics interactions, demonstrating that changes in ECM density and fibroblast composition can induce lymphatic vessel remodeling. This work has also demonstrated the potential of the model to use patient-derived cells to identify the changes induced to the lymphatic vessels. Overall, this thesis established the foundations and demonstrated the applications of the lymphatic organotypic model. Future studies are needed to better determine the influence of other TME components that could facilitate metastasis and, the use of this model could be expanded to a diverse set of research areas.