Download or read book Regulators of the Breast Tumor Immune Microenvironment written by Yeni Romero and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumors consist of a diverse population of cancer cells as well as various tumor-infiltrating immune cells, soluble factors, and extracellular matrix proteins, which are collectively known as the tumor immune microenvironment (TIME). The interactions between cancer cells and their microenvironment heavily influence tumor progression and therapeutic responses, often leading to tumor immune evasion and therapeutic resistance. Understanding these complex interactions will help develop novel strategies to target tumor cells or improve the efficacy of existing therapies. The goal of my research was to explore the role of two regulators of the tumor immune microenvironment, PD-L1 and regulatory T cells, in triple negative breast cancer (TNBC). Programmed death-ligand 1 (PD-L1) is a negative regulator of the immune system that acts as a "brake" to keep the body's immune responses under control. However, in cancer, PD-L1 expression leads to immune evasion and poor disease outcomes. In breast cancer, PD-L1 expression is most upregulated in the TNBC subtype. Under certain circumstances, transmembrane PD-L1 can be cleaved, generating a soluble form containing an intact receptor-binding domain. In my research, I investigated the cleavage of PD-L1 expressed on the surface of tumor cells. I found that a ~37-kDa N-terminal cleavage product of PD-L1 is released to the culture media. Analysis of the ~18-kDa C-terminal PD-L1 fragment demonstrated that this fragment is unstable and readily eliminated by lysosomal degradation. Furthermore, I identified ADAM10 and ADAM17, two members of the cell surface family of ADAM metalloproteases, as mediators of the cleavage of transmembrane PD-L1. Regulatory T cells (Tregs) are a subset of T cells that play a role in regulating or suppressing other immune cells. Tregs regulate the immune response to self and foreign antigens and help prevent autoimmune diseases by maintaining immune homeostasis. In cancer, Tregs are involved in tumor development and progression by inhibiting effector cells and reducing anti-tumor immunity. In TNBC, infiltration of Tregs into the TIME is often associated with resistance to anti-PD-L1 therapy and poor patient survival. Therefore, a better understanding of the mechanisms regulating the numbers of Tregs in the TIME of TNBC is necessary to tackle the problem of immunotherapy resistance. Claudin-low breast tumors are known to have increased numbers of tumor-infiltrating lymphocytes, specifically Tregs, as well as upregulated expression levels of ADAM12, an active ADAM metalloprotease. My goal was to investigate the role of ADAM12 in T cell accumulation to the tumor microenvironment in vivo using a mouse transplantation model of claudin-low breast cancer. Specifically, I investigated the accumulation of Tregs and other T cell subsets to tumors with or without expression of ADAM12. I found that the frequency of Tregs in tumor immune infiltrates was increased in tumors that lacked ADAM12 expression. Collectively, these findings give insight into the complex regulatory roles that PD-L1 and Tregs play in the breast cancer TIME.
Download or read book Immune Regulation in Breast Cancer Metastasis and Immunotherapy written by Ming-Shen Dai and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: There are significant alterations in the tumor surrounding stromal cells in addition to the cancer cells in tumor microenvironment. Tumor cells can metastasize by acquiring the ability to escape immune control and surveillance. A decline in the ability of the immune cells to recognize and kill the tumor leads to tumor relapse or metastasis after primary treatment. Comprehensive review in this chapter will be conducted to further investigate into the mechanism of immune evasion in metastatic tumor microenvironment. The immune cells, stromal cells, extracellular matrix protein/component, and their interaction will be reviewed and summarized. Breast cancer has not been previously viewed as a particularly immunogenic type of tumor. Nevertheless, immune parameters have been increasingly studied in breast cancer, and accumulating data show that they are relevant for the development and progression of this tumor type. Consequently, immunotherapies of breast cancer are now tested in different clinical trials. The prospect of immunotherapy in metastatic breast cancer will be introduced. The importance of host-targeted modulation/therapy will be increased in addition to cancer-targeted strategies. We have to better define subpopulations of breast cancer patients to optimize the immunological way to overcome the cancer metastasis.
Download or read book Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy written by Pawel Kalinski and published by Springer. This book was released on 2017-12-22 with total page 271 pages. Available in PDF, EPUB and Kindle. Book excerpt: The tumor microenvironment has become a very important and hot topic in cancer research within the past few years. The tumor microenvironment is defined as the normal cells, molecules, and blood vessels that surround and feed a tumor cell. As many scientists have realized, studying the tumor microenvironment has become critical to moving the field forward, since there are many players in a tumor’s localized and surrounding area, which can significantly change cancer cell behavior. There is a dual relationship wherein the tumor can change its microenvironment and the microenvironment can affect how a tumor grows and spreads. Tumor Microenvironment in Cancer Progression and Cancer Therapy aims to shed light on the mechanisms, factors, and mediators that are involved in the cancer cell environment. Recent studies have demonstrated that in addition to promoting tumor progression and protecting tumor cells from the spontaneous immune-mediated rejection and different forms of cancer therapeutics, tumor microenvironment can also be a target and mediator of both standard and newly-emerging forms of cancer therapeutics. Thus, the dual role of the tumor microenvironment is the integral focus of the volume. The volume highlights the bi-directional interactions between tumor cells and non-malignant tumor component during tumor progression and treatment. It also focuses on the three groups of the reactive tumor component: stromal cells, blood vessels and the infiltrating immune cells. These three groups are discussed under the lens of their role in promoting tumor growth, shielding the tumor from rejection and from standard forms of cancer therapies. They are emerging as targets and mediators of standard and new forms of potential therapy.
Download or read book Biomarkers in Breast Cancer written by Giampietro Gasparini and published by Springer Science & Business Media. This book was released on 2008-01-17 with total page 335 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.
Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-14 with total page 108 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the role of chemokines in the tumor microenvironment. Each chapter focuses on the chemokines patterns of expression, their regulation, and their roles in immune cell recruitment, as well as how they affect cancer immunity and tumorigenesis. Taken alongside its companion volumes, Tumor Microenvironment: The Role of Chemokines – Part A updates us on what we know about various aspects of the tumor microenvironment as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking a comprehensive update on research in the tumor microenvironment.
Download or read book Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies written by Manzoor Ahmad Mir and published by Elsevier. This book was released on 2022-08-10 with total page 298 pages. Available in PDF, EPUB and Kindle. Book excerpt: Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies discusses the current understanding of breast cancer tumor microenvironment components, their role in tumorigenicity and the development of therapeutic resistance, along with updates on recent advances. Presents up-to-date knowledge on the interplays of stromal components surrounding breast tumor cells Explores recent advances and trends in the molecular mechanisms of breast tumorigenesis and how to explore further molecular targets
Download or read book Extracellular Matrix Regulation of Breast Cancer Immune Microenvironment written by Giovanna Talarico and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2021-07-21 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the role of chemokines in the tumor microenvironment. Each chapter focuses on the chemokines patterns of expression, their regulation, and their roles in immune cell recruitment, as well as how they affect cancer immunity and tumorigenesis.Taken alongside its companion volumes, Tumor Microenvironment: The Role of Chemokines – Part B updates us on what we know about various aspects of the tumor microenvironment, as well as apprises us on future directions in the field. This book is essential reading for advanced cell biology and cancer biology students as well as scientists seeking an update on recent developments and research in the tumor microenvironment.
Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-02-14 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research on the role of interleukins in the tumor microenvironment. Each chapter focuses on the various ways to target the tumor microenvironment by intervention in the interleukin biology, including IL-1, IL-8, IL-21, IL-36 signaling, and more. Taken alongside its companion volumes, Tumor Microenvironment: The Role of Interleukins – Part A updates us on what we know about various aspects of the tumor microenvironment, as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.
Download or read book Regulation of Cancer Immune Checkpoints written by Jie Xu and published by Springer Nature. This book was released on 2020-03-17 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.
Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-10-29 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book focuses on the role of hematopoietic components of the tumor microenvironment. Further, it teaches readers about the roles of distinct constituents of the tumor microenvironment and how they affect cancer development. Topics include eosinophils, NK cells, γδ T cells, regulatory T Cells, Langerhans cells, hematopoietic stem cells, Mast cells, B cells and Microglia, and more. Taken alongside its companion volumes, Tumor Microenvironment: Hematopoietic Cells – Part B updates us on what we know about various aspects of the tumor microenvironment as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.
Download or read book The Link Between Inflammation and Cancer written by Angus G. Dalgleish and published by Springer Science & Business Media. This book was released on 2006-03-05 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: A link between inflammation and cancer has been established many years ago, yet it is only recently that the potential significance of this connection has become apparent. Although several examples of chronic inflammatory conditions, often induced by persistent irritation and/or infection, developing into cancer have been known for some time, there has been a notable resistance to contemplate the possibility that this association may apply in a causative way to other cancers. Examples for such progression from chronic inflammation to cancer are colon carcinoma developing with increased frequency in patients with ulcerative colitis, and the increased incidence of bladder cancer in patients suffering from chronic Schistosoma infection. Inflammation and cancer have been recognized to be linked in another context for many years, i.e., with regards to pathologies resembling chronic lacerations or 'wounds that do not heal.' More recently, the immunology of wound healing has given us clues as to the mechanistic link between inflammation and cancer, in as much as wounds and chronic inflammation turn off local cell-mediated immune responses and switch on growth factor release as well the growth of new blood vessels - angiogenesis. Both of these are features of most types of tumours, which suggest that tumours may require an immunologically shielded milieu and a growth factor-rich environment.
Download or read book Biomarkers of the Tumor Microenvironment written by Lars A. Akslen and published by Springer. This book was released on 2017-08-02 with total page 537 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews different aspects of the cancer microenvironment, and its regulation and importance for tumor progression. Practical applications, in terms of how biomarkers are increasingly included in therapy protocols, will also be discussed. Biomarkers of the Tumor Microenvironment: Basic Studies and Practical Applications is aimed at research pathologists in the cancer field, and also cancer researchers from other backgrounds, especially those using morphology techniques and models focusing on cross-talk between different cell types in tumors.
Download or read book Targeted Regulation and Cellular Imaging of Tumor Associated Macrophages in Triple Negative Breast Cancer written by Wadih Arap and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The complex interplay between immune cells and tumor cells within the tumor microenvironment (TME) can lead to disease progression. Specifically, signals generated in the TME can cause immunosuppression, promoting angiogenesis and immune evasion, which leads to tumor development. The interplay of M1 and M2 macrophage populations that coincide with these tumor markers is particularly important in the TME. Triple-negative breast cancer (TNBC) often presents as advanced disease, and these tumors are also often bereft of recognized molecular targets that can be found in other subtypes, limiting their therapeutic options. However, tumor-associated macrophages (TAMs) infiltration in TNBC is frequently observed. Moreover, a high density of TAMs, particularly M2 macrophages, is associated with poorer outcomes in various cancers, including TNBC. This provides a strong basis for exploiting TAMs as potential therapeutic targets. Specifically, efforts to increase M2 to M1 repolarization are promising therapeutic approaches in TNBC, and four recent studies wherein divergent approaches to target the M2-rich macrophage population and reverse immune subversion are described. These and similar efforts may yield promising diagnostic or therapeutic options for TNBC, a great clinical need.
Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Bidirectional Signaling Between Breast Cancer and the Tumor Microenvironment written by and published by . This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Estrogen Receptor-alpha (ER-alpha) expression in breast cancer is a standard biomarker predicting positive response to endocrine therapies targeting the ER-alpha signaling pathway. Despite ER-alpha's predictive potential, resistance to therapies remains a significant problem. Particularly in advanced disease, response rate to endocrine therapy agent tamoxifen is as low as 30%. The microenvironment in which metastatic breast cancers reside represent an unnatural context of signaling that might contribute to therapy efficacy at these sites. Indeed, ER-alpha expression is lost in one-fifth of recurrences and metastases, and the mechanism by which this occurs is unknown. This thesis work investigates the interactions of breast cancer cells with the tumor microenvironment and associated endocrine therapy resistance. Using a microfluidic co-culture model of the tumor microenvironment, I demonstrated that ER-alpha expression is reduced in response to soluble, non-estrogenic signaling from the tumor microenvironment. Multiple factors both within and between microenvironments were found to contribute to breast cancer cell growth. The complexity of the tumor microenvironment requires the identification of targets that more broadly target extracellular signaling factors. This led me to identify alterations in stromal nuclear receptors, which as targetable regulators of gene expression represent good targets for therapy. Breast cancer cells induce down-regulation of PPAR-gamma expression in stromal fibroblasts. Activation of PPAR-gamma by agonist rosiglitazone blocks stroma-induced breast cancer cell growth, implicating the inhibition of this pathway as an essential step for breast cancer cells in setting up a permissive growth environment. This bidirectional signaling model also has two major implications. For the stroma, interaction with the breast cancer cells alters the expression of a key regulator of adipogenesis, suggesting shifts in the differentiation state of the stromal fibroblasts. For the tumor cells, stroma-induced breast cancer cell growth induces endocrine therapy resistance. The loss of ER-alpha serves as a functional biomarker of this resistance, in which the ER-alpha-positive breast cancer cell line MCF-7 serves as a "biosensor" for the activity of the microenvironment. These results add to our understanding of the role of the tumor microenvironment in endocrine therapy resistance, and further implicate a number of novel targets for therapy in endocrine therapy-resistant breast cancer.
