scholarly journals Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 56
Author(s):  
Jesse D. Armitage ◽  
Hannah V. Newnes ◽  
Alison McDonnell ◽  
Anthony Bosco ◽  
Jason Waithman
Keyword(s):  
Extracellular Matrix ◽  
Immune System ◽  
Treatment Strategies ◽  
Tumour Response ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Fine Tuning ◽  
Malignant Tissue ◽  
New Treatment ◽  
Complex Architecture

Immunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (TME). The contexture of the TME is highly heterogeneous and contains a complex architecture of immune, stromal, vascular and tumour cells in addition to acellular components such as the extracellular matrix. While understanding the dynamics of the TME has been instrumental in predicting durable responses to immunotherapy and developing new treatment strategies, recent evidence challenges the fundamental paradigms of how tumours can effectively subvert immunosurveillance. Here, we discuss the various immunosuppressive features of the TME and how fine-tuning these mechanisms, rather than ablating them completely, may result in a more comprehensive and balanced anti-tumour response.

scholarly journals Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

2021 ◽  
Author(s):  
Joanna Ewa Sowa ◽  
Krzysztof Tokarski
Keyword(s):  
Glial Cells ◽  
Network Effects ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Neurological Impairment ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Biased Signaling ◽  
New Treatment

AbstractAccumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role of these immune proteins in the CNS is mirrored by the complexity of the mechanisms underlying its biological function, including biased signaling. Neurons, only in concert with glial cells, are essential players in the modulation of brain homeostatic functions. Yet, attempts to dissect these complex multilevel mechanisms underlying coordination are still lacking. Therefore, the purpose of this review is to summarize the current knowledge about mechanisms underlying chemokine regulation of neuron–glia crosstalk linking molecular, cellular, network, and behavioral levels. Following a brief description of molecular mechanisms by which chemokines interact with their receptors and then summarizing cellular patterns of chemokine expression in the CNS, we next delve into the sequence and mechanisms of chemokine-regulated neuron–glia communication in the context of neuroprotection. We then define the interactions with other neurotransmitters, neuromodulators, and gliotransmitters. Finally, we describe their fine-tuning on the network level and the behavioral relevance of their modulation. We believe that a better understanding of the sequence and nature of events that drive neuro-glial communication holds promise for the development of new treatment strategies that could, in a context- and time-dependent manner, modulate the action of specific chemokines to promote brain repair and reduce the neurological impairment.

scholarly journals Neutrophils From Patients With Invasive Candidiasis Are Inhibited by Candida albicans Biofilms

2020 ◽  
Vol 11 ◽  
Author(s):  
John F. Kernien ◽  
Chad J. Johnson ◽  
Meg L. Bayless ◽  
Jack F. Chovanec ◽  
Jeniel E. Nett
Keyword(s):  
Extracellular Matrix ◽  
Invasive Candidiasis ◽  
Nuclear Dna ◽  
Treatment Strategies ◽  
Background Level ◽  
Antifungal Drugs ◽  
Host Defenses ◽  
Device Placement ◽  
New Treatment ◽  
Net Release

Invasive candidiasis frequently involves medical device placement. On the surfaces of these devices, Candida can form biofilms and proliferate in adherent layers of fungal cells surrounded by a protective extracellular matrix. Due in part to this extracellular matrix, biofilms resist host defenses and antifungal drugs. Previous work (using neutrophils from healthy donors) found that one mechanism employed to resist host defenses involves the inhibition of neutrophil extracellular traps (NET) formation. NETs contain nuclear DNA, as well as antimicrobial proteins that can ensnare pathogens too large or aggregated to be effectively killed by phagocytosis. Given that these neutrophil structures are anticipated to have activity against the large aggregates of C. albicans biofilms, understanding the role of this inhibition in patients could provide insight into new treatment strategies. However, prior work has not included patients. Here, we examine NET formation by neutrophils collected from patients with invasive candidiasis. When compared to neutrophils from healthy participants, we show that patient neutrophils exhibit a heightened background level of NET release and respond to a positive stimulus by producing 100% more NETs. However, despite these physiologic differences, patient neutrophil responses to C. albicans were similar to healthy neutrophils. For both groups, planktonic cells induce strong NET release and biofilms inhibit NET formation. These results show that a mechanism of immune evasion for fungal biofilms translates to the clinical setting.

scholarly journals Immune abnormalities across psychiatric disorders: clinical relevance

2015 ◽  
Vol 21 (3) ◽  
pp. 150-156 ◽  
Author(s):  
Valeria Mondelli ◽  
Paola Dazzan ◽  
Carmine M. Pariante
Keyword(s):  
Bipolar Disorder ◽  
Immune System ◽  
Psychiatric Disorders ◽  
Treatment Strategies ◽  
Brain Functioning ◽  
Nervous Systems ◽  
Pathophysiological Role ◽  
Central Nervous Systems ◽  
New Treatment ◽  
The Relationship

SummaryIt is well established that the immune system can modulate brain functioning and influence behavioural processes. Awareness of communication between the immune and nervous systems has, over the years, progressively heightened interest in the relationship between psychiatric disorders and immune function. By reviewing findings from studies investigating inflammation in the periphery and in the central nervous systems, we summarise here the evidence linking inflammation to the development of depression, schizophrenia and bipolar disorder. We discuss how a pathophysiological role for inflammation has now been recognised across different psychiatric disorders, at least in a significant subpopulation of patients. Finally, we discuss a possible role for these findings in the development of future diagnostic classifications of psychiatric disorders as well as of new treatment strategies.

Is there a Role for Epigenetic Enhancement of Immunomodulatory Approaches to Cancer Treatment?

2017 ◽  
Vol 18 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Kirsty J. Flower ◽  
Sadaf Ghaem-Maghami ◽  
Robert Brown
Keyword(s):  
Expression Patterns ◽  
Immune Surveillance ◽  
Treatment Strategies ◽  
Tumour Microenvironment ◽  
The Body ◽  
Host Cells ◽  
Specific Gene ◽  
Host Immune System ◽  
A Cell ◽  
New Treatment

The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance. One such mechanism of non-efficacy or resistance is the epigenetic silencing of a specific gene required in the immunotherapy response pathway. Epigenetics is the study of the control of expression patterns in a cell via mechanisms not involving a change in DNA sequence. All tumour types show aberrant epigenetic regulation of genes involved in all the hallmarks of cancer, including immunomodulation. Inhibition of key enzymes involved in maintenance of epigenetic states is another important area of research for new treatment strategies for cancer. Could epigenetic therapies be used to successfully enhance the action of immunomodulatory agents in cancer, and are they acting in the way we imagine? An understanding of the effects of epigenetic therapies on immunological pathways in both the tumour and host cells, especially the tumour microenvironment, will be essential to further develop such combination approaches.

scholarly journals Comprehensive Characterization of Tumor Purity and Its Clinical Implications in Gastric Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Shenghan Lou ◽  
Jian Zhang ◽  
Xin Yin ◽  
Yao Zhang ◽  
Tianyi Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Comprehensive Evaluation ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Patient Specific ◽  
Validity And Reliability ◽  
Cell Functions

Solid tumour tissues are composed of tumour and non-tumour cells, such as stromal cells and immune cells. These non-tumour cells constitute an essential part of the tumour microenvironment (TME), which decrease the tumour purity and play an important role in carcinogenesis, malignancy progression, treatment resistance and prognostic assessment. However, the implications of various purity levels in gastric cancer (GC) remain largely unknown. In the present study, we used an in-silico approach to infer the tumour purity of 2,259 GC samples obtained from our hospital and 12 public datasets based on the transcriptomic data. We systematically evaluated the association of tumour purity with clinical outcomes, biological features, TME characteristics and treatment response in GC. We found that tumour purity might be a patient-specific intrinsic characteristic of GC. Low tumour purity was independently correlated with shorter survival time and faster recurrence and significantly associated with mesenchymal, invasive and metastatic phenotypes. Integrating GC purity into a clinical prognostic nomogram significantly improved predictive validity and reliability. In addition, low tumour purity was strongly associated with immune and stromal cell functions. Fibroblasts, endothelial cells and monocytes were markedly enriched in low-purity tumours, serving as robust indicators of a poor prognosis. Moreover, patients with low GC purity may not benefit more from adjuvant chemotherapy. Our findings highlight that tumour purity confers important clinical, biological, microenvironmental and treatment implications for patients with GC. Therefore, a comprehensive evaluation of tumour purity in individual tumours can provide more insights into the molecular mechanisms of GC, facilitate precise classification and clinical prediction and help to develop more effective individualised treatment strategies.

Interactions of human monocytes with TMVs (tumour-derived microvesicles)

2013 ◽  
Vol 41 (1) ◽  
pp. 268-272 ◽  
Author(s):  
Monika Baj-Krzyworzeka ◽  
Jarosław Baran ◽  
Rafał Szatanek ◽  
Bożenna Mytar ◽  
Maciej Siedlar ◽  
...  
Keyword(s):  
Immune System ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Present Review ◽  
Human Monocytes ◽  
Cellular Components

The tumour microenvironment represents a dynamic complex milieu, which includes tumour cells, cells of the immune system and other (cellular and non-cellular) components. The role of these particular ‘puzzle pieces’ may change substantially due to their mutual interactions. The present review concerns different opinions on interactions that occur between monocytes, tumour cells and TMVs (tumour-derived microvesicles).

scholarly journals Effect of Stress, Depression and Type D Personality on Immune System in the Incidence of Coronary Artery Disease

2018 ◽  
Vol 6 (8) ◽  
pp. 1533-1544 ◽  
Author(s):  
Saideh Masafi ◽  
Seyed Hassan Saadat ◽  
Katayoun Tehranchi ◽  
Roohollah Olya ◽  
Mostafa Heidari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Immune System ◽  
Coronary Artery ◽  
Treatment Strategies ◽  
Type D Personality ◽  
Type D ◽  
Artery Disease ◽  
New Treatment ◽  
The Impact

BACKGROUND: Psychoneuroimmunology (PNI) is the study of the interaction between psychological processes and the nervous and immune systems of the human body. The impact of psychological factors on the immune system and the role of this system in Coronary Artery Disease (CAD) are confirmed. Coronary Heart Disease (CHD) is arisen due to the failure of blood and oxygen to the heart tissues.AIM: The present study aimed to describe psychoneuroimmunological processes which contribute to CAD and CHD progression.METHOD: Such psychological risk factors like stress, depression and type D personality were investigated here. Psychoneuroimmunological pathways of all three mentioned risk factors were described for CAD.RESULTS: The studies review indicated that stress could be accompanied with myocardial ischemia and help to rupture. The depression involves in the transfer of stable atherosclerotic plaque to unstable, and type D personality is effective in the initial stages of a CAD.CONCLUSION: As more information on cardiovascular immunity becomes available, this will provide a better understanding and thus act as the foundation for the potential development of new treatment strategies for treatment of cardiovascular disorders.

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

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