scholarly journals Immune Cell Dysfunction as a Consequence of Severe Sepsis

10.5772/28009 ◽  
2012 ◽  
Author(s):  
William F. Carson IV ◽  
Steven L.
Keyword(s):  
Severe Sepsis ◽  
Immune Cell ◽  
Cell Dysfunction

scholarly journals Novel roles of immunometabolism and nonmyocyte metabolism in cardiac remodeling and injury

2020 ◽  
Vol 319 (4) ◽  
pp. R476-R484
Author(s):  
Alan J. Mouton ◽  
John E. Hall
Keyword(s):  
Endothelial Cells ◽  
Cardiac Remodeling ◽  
Immune Cell ◽  
Cardiac Fibroblasts ◽  
Cardiac Injury ◽  
Phenotypic Switching ◽  
Glycolytic Metabolism ◽  
Cell Dysfunction ◽  
Metabolic Switching ◽  
Review Current

Changes in cardiomyocyte metabolism have been heavily implicated in cardiac injury and heart failure (HF). However, there is emerging evidence that metabolism in nonmyocyte populations, including cardiac fibroblasts, immune cells, and endothelial cells, plays an important role in cardiac remodeling and adaptation to injury. Here, we discuss recent advances and insights into nonmyocyte metabolism in the healthy and injured heart. Metabolic switching from mitochondrial oxidative phosphorylation to glycolysis is critical for immune cell (macrophage and T lymphocyte) and fibroblast phenotypic switching in the inflamed and fibrotic heart. On the other hand, cardiac endothelial cells are heavily reliant on glycolytic metabolism, and thus impairments in glycolytic metabolism underlie endothelial cell dysfunction. Finally, we review current and ongoing metabolic therapies for HF and the potential implications for nonmyocyte metabolism.

scholarly journals Metabolic Reprogramming Induces Immune Cell Dysfunction in the Tumor Microenvironment of Multiple Myeloma

2021 ◽  
Vol 10 ◽  
Author(s):  
Shaojie Wu ◽  
Huixian Kuang ◽  
Jin Ke ◽  
Manfei Pi ◽  
Dong-Hua Yang
Keyword(s):  
Multiple Myeloma ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Metabolic Phenotype ◽  
Cell Dysfunction ◽  
Promising Therapeutic Approach ◽  
Tumor Survival

Tumor cells rewire metabolism to meet their increased nutritional demands, allowing the maintenance of tumor survival, proliferation, and expansion. Enhancement of glycolysis and glutaminolysis is identified in most, if not all cancers, including multiple myeloma (MM), which interacts with a hypoxic, acidic, and nutritionally deficient tumor microenvironment (TME). In this review, we discuss the metabolic changes including generation, depletion or accumulation of metabolites and signaling pathways, as well as their relationship with the TME in MM cells. Moreover, we describe the crosstalk among metabolism, TME, and changing function of immune cells during cancer progression. The overlapping metabolic phenotype between MM and immune cells is discussed. In this sense, targeting metabolism of MM cells is a promising therapeutic approach. We propose that it is important to define the metabolic signatures that may regulate the function of immune cells in TME in order to improve the response to immunotherapy.

scholarly journals T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective

Haematologica ◽  
2021 ◽  
Author(s):  
Fleur S. Peters ◽  
Jonathan C. Strefford ◽  
Eric Eldering ◽  
Arnon P. Kater
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
Lymphocytic Leukemia ◽  
T Cell Therapy ◽  
High Expectations ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

Cellular immunotherapeutic approaches such as chimeric antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) thus far have not met the high expectations. Therefore it is essential to better understand the molecular mechanisms of CLLinduced T-cell dysfunction. Even though a significant number of studies are available on T-cell function and dysfunction in CLL patients, none examine dysfunction at the epigenomic level. In non-malignant T-cell research, epigenomics is widely employed to define the differentiation pathway into T-cell exhaustion. Additionally, metabolic restrictions in the tumor microenvironment that cause T-cell dysfunction are often mediated by epigenetic changes. With this review paper we argue that understanding the epigenetic (dys)regulation in T cells of CLL patients should be leveled to the knowledge we currently have of the neoplastic B cells themselves. This will permit a complete understanding of how these immune cell interactions regulate T- and B-cell function. Here we relate the cellular and phenotypic characteristics of CLL-induced T-cell dysfunction to epigenetic studies of T-cell regulation emerging from chronic viral infection and tumor models. This paper proposes a framework for future studies into the epigenetic regulation of CLL-induced Tcell dysfunction, knowledge that will help to guide improvements in the utility of autologous T-cell based therapies in CLL.

scholarly journals Immune metabolism in PD-1 blockade-based cancer immunotherapy

2020 ◽  
Vol 33 (1) ◽  
pp. 17-26
Author(s):  
Alok Kumar ◽  
Kenji Chamoto
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Cancer Cell ◽  
Metabolic Regulation ◽  
Immune Cell ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

Abstract Energy metabolism plays an important role in proliferating cells. Recent reports indicate that metabolic regulation or metabolic products can control immune cell differentiation, fate and reactions. Cancer immunotherapy based on blockade of programmed cell death protein 1 (PD-1) has been used worldwide, but a significant fraction of patients remain unresponsive. Therefore, clarifying the mechanisms and overcoming the unresponsiveness are urgent issues. Because cancer immunity consists of interactions between the cancer and host immune cells, there has recently been a focus on the metabolic interactions and/or competition between the tumor and the immune system to address these issues. Cancer cells render their microenvironment immunosuppressive, driving T-cell dysfunction or exhaustion, which is advantageous for cancer cell survival. However, accumulating mechanistic evidence of T-cell and cancer cell metabolism has gradually revealed that controlling the metabolic pathways of either type of cell can overcome T-cell dysfunction and reprogram the metabolic balance in the tumor microenvironment. Here, we summarize the role of immune metabolism in T-cell-based immune surveillance and cancer immune escape. This new concept has boosted the development of combination therapy and predictive biomarkers in cancer immunotherapy with immune checkpoint inhibitors.

scholarly journals T-Cell Dysfunction as a Limitation of Adoptive Immunotherapy: Current Concepts and Mitigation Strategies

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 598
Author(s):  
Valérie Janelle ◽  
Jean-Sébastien Delisle
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Genetically Engineered ◽  
Mitigation Strategies ◽  
Cellular Immunotherapy ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

Over the last decades, cellular immunotherapy has revealed its curative potential. However, inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death, undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer, are discussed, with an emphasis on strategies used during ex vivo manipulations to limit T-cell dysfunction. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features are key to the development of improved cellular immunotherapies.

scholarly journals Dynamic Expressions of TIGIT on Splenic T Cells and TIGIT-Mediated Splenic T Cell Dysfunction of Mice With Chronic Toxoplasma gondii Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Haoran Li ◽  
Jing Zhang ◽  
Changwei Su ◽  
Xiaowei Tian ◽  
Xuefang Mei ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
Cell Function ◽  
Immune Cell ◽  
Rt Pcr ◽  
Cell Dysfunction ◽  
T Cell Dysfunction ◽  
Toxoplasma Gondii Infection ◽  
Cellular Immune

As an immunosuppressive receptor, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) play a critical part in cellular immune regulation mediated by pathogen infection. Whereas, TIGIT expression on splenic T cells in hosts infected with Toxoplasma gondii cysts has not been studied. In this study, we detected TIGIT expression and the changes of immune function in the spleen by flow cytometry and real-time PCR (RT-PCR). We found that TIGIT expression on splenic T cells increased significantly post infection. At the same time, splenic TIGIT+TCM cells were activated and transformed into TIGIT+TEM cells during the infection, and the cytotoxicity of TIGIT+ T cells was reduced in the later stage of infection. This study shows that chronic T. gondii infection can upregulate TIGIT expression on the surface of T cells and affect immune cell function.

scholarly journals Multi-model preclinical platform predicts clinical response of melanoma to immunotherapy

2019 ◽  
Author(s):  
Eva Pérez-Guijarro ◽  
Howard H. Yang ◽  
Romina E. Araya ◽  
Rajaa El Meskini ◽  
Helen T. Michael ◽  
...  
Keyword(s):  
Immune Cell ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Improve Patient Care ◽  
Immune Checkpoint Blockade ◽  
Cell Dysfunction ◽  
Clinical Observations ◽  
Genome Wide ◽  
T Cell Dysfunction ◽  
Differentiation Status

Although immunotherapy has revolutionized cancer treatment, only a subset of patients demonstrates durable clinical benefit. Definitive predictive biomarkers and targets to overcome resistance remain unidentified, underscoring the urgency to develop reliable immunocompetent models for mechanistic assessment. Here we characterize a panel of syngeneic mouse models representing the main molecular and phenotypic subtypes of human melanomas and exhibiting their range of responses to immune checkpoint blockade (ICB). Comparative analysis of genomic, transcriptomic and tumor-infiltrating immune cell profiles demonstrated alignment with clinical observations and validated the correlation of T cell dysfunction and exclusion programs with resistance. Notably, genome-wide expression analysis uncovered a melanocytic plasticity signature predictive of patient outcome in response to ICB, suggesting that the multipotency and differentiation status of melanoma can determine ICB benefit. Our comparative preclinical platform recapitulates melanoma clinical behavior and can be employed to identify new mechanisms and treatment strategies to improve patient care.

Sign in / Sign up

Export Citation Format

Share Document