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Tumor Microenvironment Regulates Tumor Expansion

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The Heterogeneity of Cancer Metabolism

The Heterogeneity of Cancer Metabolism Book
Author : Anne Le
Publisher : Springer
Release : 2018-06-26
ISBN : 331977736X
Language : En, Es, Fr & De

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Book Description :

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Tumor Microenvironment Regulation of Tumor Expansion

Tumor Microenvironment Regulation of Tumor Expansion Book
Author : Domenico Ribatti
Publisher : Academic Press
Release : 2021-04-04
ISBN : 0128228040
Language : En, Es, Fr & De

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Book Description :

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

The Role of ncRNAs non coding RNAs in Regulating Tumor Immune Microenvironment

The Role of ncRNAs  non coding RNAs  in Regulating Tumor Immune Microenvironment Book
Author : Yanyan Tang,Shiv K. Gupta,Zong Sheng Guo
Publisher : Frontiers Media SA
Release : 2022-09-14
ISBN : 2889769577
Language : En, Es, Fr & De

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Book Description :

Download The Role of ncRNAs non coding RNAs in Regulating Tumor Immune Microenvironment book written by Yanyan Tang,Shiv K. Gupta,Zong Sheng Guo, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Inflammation and Cancer

Inflammation and Cancer Book
Author : Bharat B. Aggarwal,Bokyung Sung,Subash Chandra Gupta
Publisher : Springer
Release : 2014-05-12
ISBN : 3034808372
Language : En, Es, Fr & De

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Book Description :

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

Immune Suppression and Inflammation in the Progression of Breast Cancer

Immune Suppression and Inflammation in the Progression of Breast Cancer Book
Author : Anonim
Publisher : Unknown
Release : 2008
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

Effect of Cyclosporin A on the Tumor Microenvironment

Effect of Cyclosporin A on the Tumor Microenvironment Book
Author : Yao Zhou
Publisher : Unknown
Release : 2014
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

Glioblastoma Resistance to Chemotherapy Molecular Mechanisms and Innovative Reversal Strategies

Glioblastoma Resistance to Chemotherapy  Molecular Mechanisms and Innovative Reversal Strategies Book
Author : Ramasamy Paulmurugan,Tarik F. Massoud
Publisher : Academic Press
Release : 2021-06-25
ISBN : 0128215682
Language : En, Es, Fr & De

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Book Description :

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies brings current knowledge from an international team of experts on the science and clinical management of glioblastoma chemoresistance. The book discusses topics such as molecular mechanisms of chemoresistance, experimental models to study chemoresistance, chemoresistance to drugs other than Temozolomide, and specific strategies to reverse chemoresistance. Additionally, it encompasses information on how to mitigate chemoresistance by targeted enhancement of p53 function. This book is a valuable resource for cancer researchers, oncologists, neuro-oncologists and other members of the biomedical field. Glioblastoma (GBM) is the most invasive and malignant primary brain tumor in humans with poor survival after diagnosis, therefore it is imperative that molecular and cellular mechanisms behind therapy resistant GBM cells, as well as the therapeutic strategies available to counter the resistance are comprehensively understood. Provides comprehensive, core knowledge related to the entire discipline of glioblastoma chemoresistance, from its many etiological mechanisms, to specific strategies to reverse resistance Presents current information from an international team of experts on the basic science, pre-clinical research, and clinical management of glioblastoma chemoresistance Discusses molecular and cellular mechanisms behind therapy resistant glioblastoma cells, as well as the therapeutic strategies available to counter this resistance

Patient Centered Medicine

Patient Centered Medicine Book
Author : Omur Sayligil
Publisher : BoD – Books on Demand
Release : 2017-04-12
ISBN : 9535129910
Language : En, Es, Fr & De

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Book Description :

Patient-centered medicine is not an illness-centered, a physician-centered, or a hospital-centered medicine approach. In this book, it is aimed at presenting an approach to patient-centered medicine from the beginning of life to the end of life. As indicated by W. Osler, "It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has." In our day, if the physicians and healthcare professionals could consider more than the diseased organ and provide healthcare by comforting the patients by respecting their values, beliefs, needs, and preferences; informing them and their relatives at every stage; and comforting the patients physically by controlling the pain and relieving their worries and fears, patients obeying the rules of physicians would become patients with high adaptation and participation to the treatment.

The Cancer Stem Cell Niche

The Cancer Stem Cell Niche Book
Author : Susie Prof. Nilsson
Publisher : Academic Press
Release : 2021-01-23
ISBN : 0323853269
Language : En, Es, Fr & De

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Book Description :

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

Role of ZEB1 in Macrophages During Homeostasis Inflammation and Cancer

Role of ZEB1 in Macrophages During Homeostasis  Inflammation and Cancer Book
Author : Marlies Cortés Hinojosa
Publisher : Unknown
Release : 2018
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

Overcoming Drug Resistance in Gynecologic Cancers

Overcoming Drug Resistance in Gynecologic Cancers Book
Author : Anonim
Publisher : Academic Press
Release : 2021-08-11
ISBN : 0128243007
Language : En, Es, Fr & De

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Book Description :

Overcoming Drug Resistance in Gynecologic Cancers provides up-to-date information related to important gynecologic cancers and focuses on mechanisms of drug resistance, genetics, signaling, immunology, health disparities, nanotechnology, economic considerations and financial impacts. The book covers not only drug resistance but also important means to reverse resistance both in the laboratory and clinic. The book discusses topics such as lifestyle, nutrition and risk of gynecologic cancers, the financial impact of drug resistance, chemosensitizing agents and targeted therapies in cervical, endometrial and ovarian cancer, immunotherapy to overcome drug resistance, and genetic polymorphisms in gynecologic cancers. Additionally, it discusses ethnic and racial health disparity perspectives and future developments in chemosensitizing activities to reverse drug resistance in gynecologic cancers. It is a valuable resource for cancer researchers, oncologists, clinicians and other biomedical field members who are interested in new approaches to improve chemotherapy outcome in patients with gynecologic cancers. Provides a comprehensive resource with all the details needed for readers to understand and follow information Encompasses schematics, diagrams and flow charts in all chapters to help readers easily follow critical information Presents tables and figures especially developed to summarize the information with appropriate statistical rigor and to show details of clinical specimens such as pathological, radiological characteristics, and/or laboratory biomarkers

Tumor Microenvironment

Tumor Microenvironment Book
Author : Alexander Birbrair
Publisher : Springer Nature
Release : 2020-02-08
ISBN : 3030357236
Language : En, Es, Fr & De

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Book Description :

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.

Targeting the Tumor Microenvironment for a More Effective and Efficient Cancer Immunotherapy

Targeting the Tumor Microenvironment for a More Effective and Efficient Cancer Immunotherapy Book
Author : Salem Chouaib,James Lorens
Publisher : Frontiers Media SA
Release : 2020-07-02
ISBN : 2889638170
Language : En, Es, Fr & De

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Book Description :

Download Targeting the Tumor Microenvironment for a More Effective and Efficient Cancer Immunotherapy book written by Salem Chouaib,James Lorens, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Basic Radiotherapy Physics and Biology

Basic Radiotherapy Physics and Biology Book
Author : David S. Chang,Foster D. Lasley,Indra J. Das,Marc S. Mendonca,Joseph R. Dynlacht
Publisher : Springer
Release : 2014-09-19
ISBN : 3319068415
Language : En, Es, Fr & De

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Book Description :

This book is a concise and well-illustrated review of the physics and biology of radiation therapy intended for radiation oncology residents, radiation therapists, dosimetrists, and physicists. It presents topics that are included on the Radiation Therapy Physics and Biology examinations and is designed with the intent of presenting information in an easily digestible format with maximum retention in mind. The inclusion of mnemonics, rules of thumb, and reader-friendly illustrations throughout the book help to make difficult concepts easier to grasp. Basic Radiotherapy Physics and Biology is a valuable reference for students and prospective students in every discipline of radiation oncology.

Tumor Microenvironment

Tumor Microenvironment Book
Author : Alexander Birbrair
Publisher : Springer Nature
Release : 2020-02-06
ISBN : 3030355829
Language : En, Es, Fr & De

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Book Description :

Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on how different signaling pathways are important in the tumor microenvironment. Multiple signaling pathways are covered, including S1P, neuregulin, Notch, erythropoietin, Rho-ROCK, mTOR, 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: Signaling Pathways – 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.

Histopathology

Histopathology Book
Author : Supriya Srivastava
Publisher : BoD – Books on Demand
Release : 2018-09-19
ISBN : 178923686X
Language : En, Es, Fr & De

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Book Description :

This book, "Histopathology-An Update" is a comprehensive book that deals with the latest advances in the field of histopathology. This book will be of help to pathologists, clinicians and researchers in the latest update in histopathology of various organs.

Tumor Microenvironments in Organs

Tumor Microenvironments in Organs Book
Author : Alexander Birbrair
Publisher : Springer Nature
Release : 2020-02-06
ISBN : 3030362140
Language : En, Es, Fr & De

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Book Description :

Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the tumor microenvironment in over thirty human organs, including the parathyroid gland, heart, intestine, testicles, and more. Taken alongside its companion volumes, these books update us on what we know about the different aspects of the tumor microenvironments in distinct organs as well as future directions. Tumor Microenvironments in Organs: From the Brain to the Skin – 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.

Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer

Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer Book
Author : Michail Ignatiadis,Christos Sotiriou,Klaus Pantel
Publisher : Springer Science & Business Media
Release : 2012-04-23
ISBN : 3642281605
Language : En, Es, Fr & De

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Book Description :

This important book provides up-to-date information on a series of topical issues relating to the approach to minimal residual disease in breast cancer patients. It first explains how the study of minimal residual disease and circulating and disseminated tumor cells (CTCs/DTCs) can assist in the understanding of breast cancer metastasis. A series of chapters then discuss the various technologies available for the detection and characterization of CTCs and DTCs, pinpointing their merits and limitations. Detailed consideration is given to the relevance of CTCs and DTCs, and their detection, to clinical research and practice. The role of other blood-based biomarkers is also addressed, and the closing chapters debate the challenges facing drug and biomarker co-development and the use of CTCs for companion diagnostic development. This book will be of interest and assistance to all who are engaged in the modern management of breast cancer.

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 Book
Author : So-Hyun Park
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.

Regulatory Mechanism of Myeloid Derived Suppressor Cell Activity

Regulatory Mechanism of Myeloid Derived Suppressor Cell Activity Book
Author : Cesar Alexander Corzo
Publisher : Unknown
Release : 2010
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

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.