Implications Of Immune Landscape In Tumor Microenvironment
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Author | : Selvarangan Ponnazhagan |
Publisher | : Frontiers Media SA |
Total Pages | : 190 |
Release | : 2024-10-01 |
Genre | : Medical |
ISBN | : 2832555152 |
Tumor microenvironment (TME) plays an important role in immunosuppressive mechanisms that result in immune editing and treatment resistance. Elucidating the diversity of stromal and immune cell distribution, polarization, and changes in their gene expression signatures will enable a better understanding of key events to improve treatment and prognosis. With the onset of immune checkpoint inhibitors (ICIs) in clinics for patients with solid tumors and hematologic malignancies, immunotherapy has taken a new direction in cancer management, especially as combination therapies. However, limitations encountered with the use of ICIs, including toxicity and immune-related adverse events (irAE) indicate the need to understand multiple regulatory mechanisms at both cellular and molecular levels that alter the immune landscape of the TME. Since predominant changes in the immune landscape occur at the TME, focussed deliberation on these events will provide a comprehensive understanding on this topic for scientists in the fields of basic, translational, and clinical cancer immunology. The heterogeneity of TME and complex immune landscape pose major challenges in the treatment of solid tumors. Thus, integrative approaches, which relate immune mechanisms in the TME to that of peripheral and systemic immune signatures are essential to improve our understanding of the disease complexity and possibly improve immunotherapy outcomes. Such multiparametric studies should combine advances in current understanding of cancer immunobiology with powerful technologies, such as single-cell and spatial transcriptomics, and high dimensional flow cytometry that rapidly expand our ability to explore these interactions. Notably, tumor heterogeneity and inflammatory mediators in the TME vary significantly in neoplasms based on mutational load, lymphocyte infiltration, expression of checkpoint molecules, soluble inhibitors, and tumor cell metabolism. Overall, connecting key events to immune signatures that conform to a consensus will provide a benchmark to delve further into this important topic. Other parameters such as myeloid and lymphoid cell polarization to alter the immune homeostasis at the TME, favoring a tumor-supportive milieu would provide a macroscopic picture that may help guide treatment choices for more refined personalized tumor immunotherapy.
Author | : Nan Zhang |
Publisher | : Frontiers Media SA |
Total Pages | : 297 |
Release | : 2023-10-24 |
Genre | : Medical |
ISBN | : 2832536301 |
The tumor microenvironment (TME) plays a critical role in tumor proliferation, progression, and therapeutic responses. TME is a complex network of cancer cells, stromal cells, and, most importantly, infiltrating immune cells. Cancer cells regulate numerous biological functions through direct or indirect interaction with TME components. Emerging evidence suggests that TME crucially influences the response to both chemotherapy and immunotherapy. As scientific research has entered the big data era with the fast development of high-throughput sequencing technologies, machine learning has been gradually widely applied to extract important knowledge from big data bioinformatics. Thus, characterizing the TME landscape in cancer and identifying different immune-related TME phenotypes using machine learning-based bioinformatics analyses, in vitro experiments, and in vivo experiments are of great interest and significance.
Author | : Peter P. Lee |
Publisher | : Springer Nature |
Total Pages | : 326 |
Release | : 2020-03-25 |
Genre | : Medical |
ISBN | : 303038862X |
This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.
Author | : Noha Mousaad Elemam |
Publisher | : Frontiers Media SA |
Total Pages | : 144 |
Release | : 2023-09-13 |
Genre | : Medical |
ISBN | : 2832534929 |
One of the current challenges and failures of immunotherapy is in part due to the complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. The TME consists of various cell types (tumor cells, fibroblasts, endothelial cells, and immune cells), soluble signaling molecules (cytokines, growth factors, and chemokines), and extracellular matrix. On another note, metabolic disturbances in various TME components, such as hypoxia, acidosis, lactate accumulation, and nutrient deprivation, can play a critical role in the tumor progression. Furthermore, genetic and epigenetic dysfunctions are known to be part of the characteristics of cancer development. The immune cells could have a pro- or anti-tumor role in the TME, and their activity might vary in the context of different cancers. Both innate and adaptive immune cells interact with tumor cells through direct contact or through chemokines and cytokines signaling, shaping the tumor's activity and response to therapy.
Author | : Petranel T. Ferrao |
Publisher | : Frontiers Media SA |
Total Pages | : 186 |
Release | : 2019-11-01 |
Genre | : |
ISBN | : 288963115X |
Cancer cells can change and adapt, especially within the host environment; a phenomenon known as cancer plasticity. Several factors, including the immune system can influence, and be influenced by, cancer plasticity which in turn can impact upon patient responses to treatment. As such, we currently face several challenges for implementing combination therapies as effective cancer treatment strategies. We have compiled a topic with a number of articles that emphasize the various aspects of cancer plasticity, describing in particular the important role of the tumor microenvironment. As we embark on a new era of precision medicine with multi-modal therapies for improving patient outcomes, this topic highlights some relevant points for consideration that are pertinent to the incorporation and effective use of new treatments as part of cancer treatment regimens, including immune-modulating drugs.
Author | : Alexander Hao Lee |
Publisher | : |
Total Pages | : 0 |
Release | : 2023 |
Genre | : |
ISBN | : |
Glioblastoma (GBM) is the most common malignant tumor in the central nervous system and has poor patient survival rates. Unlike other cancers, immune checkpoint therapies, such as PD-1 checkpoint blockade, have been largely ineffective in GBMs for several reasons: an immunosuppressive tumor microenvironment, a lack of suitable neoantigens, and poor intratumoral T cell infiltration and activity. However, there is evidence that using anti-PD-1 therapy in the neoadjuvant setting may generate a more robust anti-tumor immune response, though characterizing how the GBM tumor microenvironment changes with such therapy is incomplete. As such, we performed high dimensional analysis using CyTOF mass cytometry and single-cell RNAsequencing to study the intratumoral immune populations in GBM patients treated with or without neoadjuvant anti-PD-1 therapy. Characterizing PD-1 expressing tumor infiltrating T cell populations showed that PD-1 was associated with markers of T cell activation and dysfunction regardless of treatment and that this association existed less strongly in peripheral PD-1 expressing T cells. We studied the effects of neoadjuvant anti-PD-1 therapy on a large patient cohort of tumor infiltrating immune cells and found that neoadjuvant anti-PD-1 therapy significantly increased the proportion of several intratumoral T cell sub-populations, including a TCF7-expressing progenitor exhausted population. Downstream effects of neoadjuvant anti-PD-1 therapy on T cells, namely increased production of IFN-g, included transcriptionally altering the myeloid and dendritic cell populations to be more immune suppressive but also potentially more vulnerable to other immune checkpoint therapies, specifically anti-TIGIT and anti-CTLA-4 therapies. Due to the impact of neoadjuvant anti-PD-1 therapy on intratumoral T cell populations, we examined whether we could detect tumor-reactive T cells by cloning TCRs from transcriptionally defined populations in a patient treated with neoadjuvant anti-PD-1 and testing reactivity to the patient-derived gliomasphereline. Among TCRs cloned, we discovered that T cells arising from the activated and exhausted population showed tumor reactivity, suggesting that utilizing transcriptional phenotypes can guide selection of potential tumor-reactive TCRs in GBM patients treated with neoadjuvant anti-PD-1 therapy. In conclusion, neoadjuvant anti-PD-1 therapies alters the immune landscape in these tumors and can be potentially used in combination with other immunotherapies to more effectively treat this malignancy.
Author | : Fumito Ito |
Publisher | : Elsevier Health Sciences |
Total Pages | : 271 |
Release | : 2018-09-03 |
Genre | : Medical |
ISBN | : 0323549500 |
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.
Author | : Marie-Caroline Dieu-Nosjean |
Publisher | : Humana Press |
Total Pages | : 289 |
Release | : 2018-09-05 |
Genre | : Medical |
ISBN | : 9781493987085 |
This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.
Author | : Gianfranco Baronzio |
Publisher | : Springer Science & Business Media |
Total Pages | : 247 |
Release | : 2009-04-10 |
Genre | : Medical |
ISBN | : 1402095767 |
In the post-genomic era, cancer is a genetic disease. However, cancer genotype does not always equal cancer phenotype. Cancers with the same genetic abnormalities don’t always behave the same. Understanding and eradicating cancers will require an appreciation for cancer’s ecology. This book is the first to comprehensively explore and critically appraise cancer microenvironments and host interactions with an eye towards exploiting our understanding for new treatments. The team of contributors share amongst them impressive experiences at the laboratory bench and in the clinic. These physician-scientists have dedicated themselves to the tension between the urgency for cures and the technical challenges of discovery. The target audience includes clinical oncologists, clinical hematologists, research oncologists, research hematologists, immunologists, stem cell researchers, oncology and hematology fellows (trainees), oncology educators (graduate and undergraduate levels), and course book for graduate students and undergraduate students.
Author | : Fei Yu |
Publisher | : Frontiers Media SA |
Total Pages | : 170 |
Release | : 2023-09-25 |
Genre | : Medical |
ISBN | : 2832534112 |