Download or read book Novel Mediators of Anti tumor Immunity written by and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Mechanisms of Photodynamic Therapy Induced Anti Tumor Immunity written by Minan Wang and published by . This book was released on 2013 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Photodynamic therapy (PDT) has long been shown to be capable of killing malignant cells, causing shut down of tumor microvasculature, and induction of host immune response. The therapeutic efficacy of PDT is dependent on CD8+ T cells. Activation of tumor-antigen-specific CD8+ T cells requires cross-presentation and cross-priming by dendritic cells (DCs). The cytokine secretion profile of DCs dictates different CD4+ T cell responses, which are critical for CD8+ T cell differentiation and activation. However, the development of CD4+ T cells in the setting of PDT treatment is unclear and controversial. Therefore, to improve PDT efficacy in treating aggressive and metastatic disease, it is imperative to understand the mechanisms of how PDT treatment activates DCs, triggers T cell responses, and the role of responding T cells in PDT efficacy and induction of anti-tumor immunity. We show that PDT-generated tumor cell lysate (PDTTCL) can activate bone marrow-derived dendritic cells (BMDCs) efficiently by upregulation of co-stimulatory molecules and induction of pro-inflammatory cytokines as well as chemokines that are critical mediators for shaping anti-tumor immune response by enhancing CD8+ T cell responses. IL-1©Ø is required for DC cross-priming of interferon (IFN)-©Đ-producing CD8+ T cells by PDTTCL. PDTTCL-induced IL-1©Ø is produced in a toll-like receptor (TLR)-dependent but NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-inflammasome-independent pathway. In addition, PDTTCL induction of IL-1©Ø precursor synthesis is also dependent upon serine proteases. Our results revealed that PDTTCL induces IL-1©Ø maturation in a novel signaling pathway dependent on membrane-bound protease(s). We found that NF-©®B plays a dual role in PDT induction of IL-1©Ø synthesis and activation.^Our study contributes to the mechanisms of how PDT enhances tumor cell immunogenicity to promote DC activation, providing the potential means to optimize CD8+ T cell responses and improve clinical PDT efficacy. The mechanisms of how IL-1©Ø contributes to PDT efficacy are not fully understood. In addition to its critical role in DC cross-priming of CD8+ T cells, IL-1©Ø also plays a vital role in Th17 cell differentiation and development. We further investigated the poorly characterized CD4+ T cell responses elicited by PDT. CD4+ T cell lineage differentiation is driven by cytokines generated after DC activation. By examining the cytokine profile of PDTTCL stimulated BMDCs, we found a novel CD4+ Th17 cell response following in situ PDT treatment. The major cytokine secreted by Th17 cells is IL-17, which plays a crucial role in PDT-induced antitumor immunity. A better understanding about how DCs are matured and activated by PDTTCL allows us to further exploit PDT in combination with DC vaccine against aggressive tumor model. We significantly improved PDT efficacy in treating aggressive tumor by combining DC vaccine and TLR8/8 agonist, providing promising strategy using PDT to combat secondary disease in clinics. In PDT combination therapy treated tumor bearing mice, we show that the efficacy of PDT combination therapy is dependent on CD4+ T cells, CD8+ T cells and natural killer (NK) cells. Due to the complex cross-talk of DCs, NK and T cells, we believe it is essential to study the role of them at different stages after PDT to better understand how their roles may change during disease progression, and to optimize PDT efficacy by exploiting them appropriately.
Download or read book Impact of Tumor Hypoxia on Immune Response Implication for Radiotherapy and Anti Tumor Immunity written by Aditi Murthy and published by . This book was released on 2019 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor hypoxia occurs due to the increase in demand for oxygen by the rapidly growing tumor cells together with reduction in the supply of oxygen due to malformed and dysfunctional tumor vasculature. Tumor hypoxia offers resistance to radiotherapy (RT) and chemotherapy. Interestingly, a new paradigm has emerged suggesting that hypoxia may also suppress immunotherapy, however the mechanisms behind this observation remain undetermined. Our laboratory and others have demonstrated that IFN?, an important immunotherapeutic mediator, conditions the tumor microenvironment and is important for the efficacy of radiotherapy. As a result, we hypothesized that hypoxia could inhibit the anti-tumor responses mediated by IFN? resulting in a decrease of radiotherapy efficacy. We demonstrated a possible mechanism of hypoxia induced immune-escape. Hypoxia could be reducing the ability of cells to respond to IFN?. We observed that hypoxia downregulated MHC I protein expressed by murine tumor cell lines thus evading immune recognition by immune cells. To test hypoxia induced inhibition we demonstrated in vitro that hypoxia inhibited the induction of IFN?-stimulated genes in multiple human and murine tumor cell lines and peripheral blood mononuclear cells suggesting hypoxia could inhibit the responsiveness to IFN?. Hypoxia also inhibited proliferation and effector function of antigen specific T cells in vitro further demonstrating suppressive effect of hypoxia on T cells which are essential mediators of anti-tumor immune response. We utilized Colon-38, a murine colon adenocarcinoma tumor model, and measured intratumoral hypoxia by both flow cytometry and fluorescence microscopy using a monoclonal antibody that detects hypoxia-induced 2-nitroimidazole adducts from the drug EF5. We identified immune cells that exist in hypoxic tumor regions. We used this drug to demonstrate a time dependent increase of hypoxia within untreated Colon-38 tumors. Irradiation resulted in a decrease in total tumor hypoxia. Furthermore, preliminary results from RNA-seq analysis of hypoxic and adjacent normoxic tumor samples obtained by laser capture microdissection have demonstrated up-regulation of angiogenic and tissue developmental pathways in hypoxic tumor areas compared to normoxic areas. However, we did not see any significant differences in the expression of IFN? or IFN?-dependent genes between the two regions. Taken together this data would suggest that Colon38 tumors are radiosensitive and to overcome hypoxia they up regulate angiogenic pathways. To mimic a clinically relevant model we examined the impact of two different immune modulators?MTLL2 and IL-12 on the efficacy of RT. MTLL2 is a combination of a CCR2 inhibitor and monomethyl fumarate (MMF). As mentioned earlier radiotherapy generates an effective anti-tumor immune response however it also stimulates the infiltration of CCR2 expressing immunosuppressive cells (inflammatory monocytes) into the tumor, which can dampen this ongoing immune response. Therefore, we hypothesize that MTTL2 would prevent the entry of immunosuppressive cells and simultaneously maintain the ongoing anti-tumor immune response further enhancing the efficacy of radiotherapy. We optimized the concentration of MTLL2 administered to Colon38 tumor bearing mice one day prior to radiation therapy treatment that resulted in reduced tumor growth compared to untreated unirradiated control mice. MTLL2 administration also resulted in increase in percentage of CD8+, CD4 + and NK cells in peripheral blood and fewer circulating CCR2+ monocytes suggesting an enhanced immune response compared to untreated controls. We also investigated the impact of a potent cytokine IL-12 on tumor hypoxia. We have previously shown that IL-12 can normalize tumor vasculature. Therefore, by using a combination of RT and IL-12 immunotherapy we can generate a multi-pronged approach targeting tumor hypoxia and enhancing anti-tumor effector responses mediated by IFN?. We proposed that tumors that are less hypoxic ( e.g. after RT and immunotherapy) are more conducive to IFN? and T cell responses, resulting in enhanced tumor control. We used a model of Colon38 tumor cells stably transfected to express IL-12 constitutively. Irradiating Colon38/IL-12 tumors 7 days post-tumor inoculation resulted in significant reduction in intratumoral hypoxia compared to parental control tumors. We also investigated tumor growth in C57BL6/J mice with clones of Colon38/IL12 tumor cells producing varying amounts of IL-12 to optimize the amount of IL-12 required for tumor rejection. These studies demonstrate different combinatorial therapies that can alter the tumor microenvironment and enhance the anti-tumor immune response.
Download or read book Inflammation and Cancer written by Bharat B. Aggarwal and published by Springer. This book was released on 2014-05-12 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Janeway s Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.
Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
Download or read book Immunotherapy written by Aung Naing and published by Springer Nature. This book was released on 2022-01-01 with total page 445 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.
Download or read book Guide to Immunotherapy written by Suzanne L. Walker and published by . This book was released on 2018-10 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Lipid Metabolism in Tumor Immunity written by Yongsheng Li and published by Springer. This book was released on 2022-04-03 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on lipid metabolism in tumor immunity, covering the application of lipidomics in tumor immunity and all aspects of lipid metabolism in tumor microenvironment. During the progression of tumors, tumor cells and immune cells interact in a dynamic microenvironment. Targeting the immune system has a high potential for treating cancer. However, due to the high heterogeneity of the tumor microenvironment, only a small percentage of patients experience such clinical benefits of tumor immunotherapy. Therefore, understanding the tumor microenvironment is crucial for tumor immunity. Recently, lipid metabolism is an emerging research direction and contributes to cell survival and biofunctions in tumor microenvironment, which is of great interest and significance to be elucidated. This book provides the doctors, researchers, and scientists with a cutting-edge overview of the lipid metabolism and its role in tumor immunity. It also yields benefits for pharmaceutical companies regarding drug discovery.
Download or read book Systems Biology of Cancer written by Sam Thiagalingam and published by Cambridge University Press. This book was released on 2015-04-09 with total page 597 pages. Available in PDF, EPUB and Kindle. Book excerpt: An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
Download or read book HSPs Ambiguous Mediators of Immunity written by Stuart Keith Calderwood and published by Frontiers Media SA. This book was released on 2017-05-11 with total page 94 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heat shock proteins (HSPs) were discovered as polypeptides induced by stress that can be found in all kingdoms of cellular organisms. Their functions were, a first enigmatic and these proteins were thus classified by molecular weight, as in—Hsp27, Hsp70, Hsp90, Hsp110. More recently, each of these size-classified molecules has attributed a role in protein folding, and they thus came to be known, as a class, as molecular chaperones. However, the they possess properties beyond chaperoning. Indeed, their discovery in the extracellular spaces suggested roles in regulation of the immune responses.
Download or read book Methods in Cancer Immunity and Immunotherapy 2022 written by Manel Juan and published by Frontiers Media SA. This book was released on 2023-10-27 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Research Topic is part of the “Methods in Immunology” series. Please submit your article to the Research Topic that best suits the focus of your research. Introduction and general guidelines: This series aims to highlight the latest experimental techniques and methods used to investigate fundamental questions in Immunology research, with a focus on Cancer Immunity and Immunotherapy.
Download or read book Chemokines and Cancer written by Barrett Rollins and published by Springer Science & Business Media. This book was released on 1999 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the introduction of microscopy, pathologists have noted tumor infiltration by inflammatory cells and presumed that this represents the host's attempt to reject its tumor. Recent advances in the molecular biology of inflammation have revealed the signals involved in attracting inflammatory cells to tumors and, for the most part, these signals are mediated by chemokines and their receptors. Chemokines are low molecular weight proteins that attract and activate specific subsets of leukocytes to the exclusion of others.
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 The Na H Exchanger written by Larry Fliegel and published by New York : Springer. This book was released on 1996 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Natural Killer Cell Interactome in the Tumor Microenvironment Basic Concepts and Clinical Application written by Martin Villalba and published by Frontiers Media SA. This book was released on 2020-07-02 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Immune Checkpoint Inhibitors in Cancer written by Fumito Ito and published by Elsevier Health Sciences. This book was released on 2018-09-03 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Get a quick, expert overview of the latest clinical information and guidelines for cancer checkpoint inhibitors and their implications for specific types of cancers. This practical title by Drs. Fumito Ito and Marc Ernstoff synthesizes the most up-to-date research and clinical guidance available on immune checkpoint inhibitors and presents this information in a compact, easy-to-digest resource. It’s an ideal concise reference for trainee and practicing medical oncologists, as well as those in research. Discusses the current understanding of how to best harness the immune system against different types of cancer at various stages. Helps you translate current research and literature into practical information for daily practice. Presents information logically organized by disease site. Covers tumor immunology and biology; toxicities associated with immune checkpoint inhibitors; and future outlooks. Consolidates today’s available information on this timely topic into one convenient resource.
