Immune escape and ageing of the immune system compromises the immune response to tumor antigens

2014 ◽  
pp. 415-432
Author(s):  
Ludmila Müller ◽  
Graham Pawelec
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Tumor Antigens ◽  
Immune Escape

scholarly journals SARS-CoV-2 Infection, COVID-19, and long covid: Saga of erratic immune response, waning immunity, and immune system failure

2021 ◽  
Vol 5 (1) ◽  
pp. 077-086
Author(s):  
Nikhra Vinod
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Disease Transmission ◽  
Neutralizing Antibodies ◽  
Evolutionary Dynamics ◽  
Immune Escape ◽  
Clinical Manifestations ◽  
System Failure ◽  
S Protein ◽  
Adaptive Mutations

Introduction - evolution of SARS-CoV-2 variants: With the unrestrained pandemic for over last one-and-half year, SARS-CoV-2 seems to have adapted to its habitat, the human host, through mutations that facilitate its replication and transmission. The G variant incorporating D614G mutation, potently more transmissible than the ancestral virus arose during January 2020 and spread widely. Since then, various SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with higher infectivity or virulence or both, have evolved on the background of G variant, and spread widely. SARS-CoV-2 infection and the immunodynamics: As the virus becomes more transmissible, its lethality may drop. Apart from the humoral immunity, T-cell recognition from a previous SARS-CoV-2 infection or vaccination may modify the disease transmission correlates and its clinical manifestations. On the other hand, the immunity generated may reduce probability of re-infection as well as limit evolution of adaptive mutations, and emergence of highly infectious and immune-escape variants. There are complex issues related to the SARS-CoV-2 evolutionary dynamics and host’s immunodynamics. Trending etiopathoimmunological correlates: The evolution potential of SARS-CoV-2 is limited because of proofreading function of nsp14. The S protein mutations affect transmissibility, virulence, and vaccine efficacy. The D614G mutation in G variant with higher infectivity has turned the Chinese epidemic into a pandemic. Other SARS-CoV-2 variants, such as Alpha, Beta, Gamma, and Delta seem to have evolved as result of adaptation to selective pressures during periods of prolonged infections and subsequent transmission. Further, there is issue of convergent association of mutations. Basics of immunity and immune system failure: The nature of the immune response after natural SARS-CoV-2 infection is variable and diverse. There are pre-existing neutralizing antibodies and sensitized T cells elicited during previous infection with seasonal CoVs influencing the disease susceptibility and course. The virus has evolved adaptive mechanisms to reduce its exposure to IFN-I and there are issues related to erratic and overactive immune response. The altered neutralizing epitopes in the S protein in SARS-CoV-2 variants modify the immune landscapes and clinical manifestations. Conclusion: current scenarios and prospects: Presently, the SARS-CoV-2 infection is widespread with multiple evolving infectious variants. There is probability of its transition from epidemic to endemic phase in due course manifesting as a mild disease especially in the younger population. Conversely, the pandemic may continue with enhanced disease severity due to evolving variants, expanded infection pool, and changing immunity landscape. There is need to plan for the transition and continued circulation of the virus during the endemic phase or continuing pandemic for indefinite period.

scholarly journals THE MECHANISMS OF IMMUNE ESCAPE BY HEPATITIS B VIRUS

2017 ◽  
Vol 72 (6) ◽  
pp. 408-419 ◽  
Author(s):  
M. V. Sokolova ◽  
M. V. Konopleva ◽  
Т. A. Semenenko ◽  
V. G. Akimkin ◽  
A. V. Tutelyan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
Cell Functions ◽  
Adaptive Immune ◽  
B Virus

The high prevalence of the hepatitis B virus (HBV) in population occurs mainly due to numerous mechanisms formed in the process of the virus evolution, contributing to its survival under immunological pressure. The review presents the most complete systematization and classification of various HBV protective mechanisms basing on their influence on different parts of congenital and adaptive immune response. The analysis of literature data allows for the conclusion that two basic principles underlie the mechanisms: the strategy of the «stealth virus» (virus’s escape from recognition by the immune system) and strategy of immunosuppression. The stealth virus strategy is performed as follows: special strategy of the HBV replication which prevents the recognition by the receptors of congenital immune system; occurrence of the vaccine escape mutants; isolation of the virus in host cells and tissues providing its inaccessibility to T-cells along with hyperproduction of subviral particles as traps for specific antibodies. The core principle of the immunosuppression implemented in hepatitis B therapy is based on the phenomenon of the viral apoptotic mimicry. The result of this interaction strategy is dysfunction of NK and NKT-cells, inactivation of dendritic cell functions, and suppression of the adaptive immune response. The review demonstrates that interaction between HBV and the immune system of the macro organism is in some kind of «dynamic equilibrium» depending on numerous factors. Specific molecular targets of the viral impact are described. We propose to expand the research on the influence of the host’s genetic factors on the development of congenital and adaptive immune response against HBV, especially during the real infectious process which results in the improvement of approaches to the therapy by developing personalized treatment methods.

scholarly journals Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Andrzej Eljaszewicz ◽  
Małgorzata Wiese ◽  
Anna Helmin-Basa ◽  
Michal Jankowski ◽  
Lidia Gackowska ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Adaptive Response ◽  
Immune Escape ◽  
Cell Formation ◽  
Neoplastic Disease ◽  
Neoplastic Tissue ◽  
Predominant Component ◽  
Induction Of Tolerance ◽  
Naive T Lymphocytes

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

The anti-tumour immune response after radiofrequency ablation of colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14540-e14540
Author(s):  
Katia Lemdani ◽  
Claude Capron ◽  
Johanne Seguin ◽  
Nathalie Mignet ◽  
Vincent Boudy ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiofrequency Ablation ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Immune Escape ◽  
Liver Tumors ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Strong Immune Response

e14540 Background: Results of radiofrequency ablation (RFA), increasingly used to treat liver tumors, are compromised by local and systemic relapse. Hyperthermia related cancer cells death, release of tumor antigens and expression of danger signals activate a tumor-specific T-cells response. This effect remains ineffective to avoid recurrence. Therefore we propose to combine RFA with an activation of a solid immune antitumor response as curative treatment of a colorectal (CRC) metastatic disease in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor. In two distinct clinical situations, distant macroscopic or microscopic tumors were established as metastases before or at the time of RFA. Immune response was modulated by an injection in situof a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting dendritic cells. In the group of mice with large far lesions this strategy was combined with immune checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of lymphocyte infiltration in tumors and systemic immunity through specific TNF- α and IFN-y expression in spleen and draining lymph nodes. Results: The in situ immunogel injection after RFA resulted in a prolonged survival of mice. Regression of distant lesions was related to a strong systemic antitumor immune response and a great improvement of tumor infiltration by specific cytotoxic lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without any treatment. Immune escape of large secondary lesions was reversed by association of RFA-immunogel vaccination with a systemic check point blockade, separately ineffective. Conclusions: Validation of this strategy, combining RFA of liver metastases and activation of a strong immune response controlling the residual disease, could result in a clinical assay including this approach within the standard treatment of CRC. Furthermorethe powerful synergy between RFA-in situ immunomodulation as a starter treatment and checkpoint blockade ineffective alone in CRC or after single RFA, allows reconsidering the use of immune checkpoint inhibitors in metastatic microsatellite stable CRC.

scholarly journals Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Claudia Palena ◽  
Jeffrey Schlom
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Tumor Growth ◽  
Cancer Vaccines ◽  
Cell Activation ◽  
Immune Cell ◽  
Immune Escape ◽  
Adaptive Immune Response ◽  
Tumor Immune Escape ◽  
Multiple Observations

Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

HIV-1 POPULATION DYNAMICS IN VIVO: IMPLICATIONS FOR PATHOGENESIS, EFFECT OF CYTOKINE AND THERAPY STRATEGY

2004 ◽  
Vol 12 (03) ◽  
pp. 315-333
Author(s):  
JIE LOU ◽  
ZHIEN MA ◽  
MEIZHI LOU ◽  
YIMING SHAO
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Escape ◽  
Interleukin 2 ◽  
Human Immune System ◽  
Therapy Strategy ◽  
The Impact ◽  
Hiv 1

In this paper, we present a dynamical model to study the spread of HIV-1 in vivo. Our goal is to better understand the interaction between HIV-1 and the human immune system. Making use of the Hill function, we describe two kinds of processions occurring in the immune response: the activation interactions or inhibitory interactions occurring between different components in the immune response, and the autocatalytic maintenance of the CD4+ T cells and CD8+ T cells populations. We also consider the impact of the cytokine interleukin-2 (IL-2) and the CD8 antiviral factor (CAF) on HIV-1 infection. Through numerical simulations we get several results. First, we find that the effects of IL-2 and CAF in the treatment for the infected are limiting. Namely, the curative effect will not always increase along with the dose of IL-2 or CAF or both. The increasing trend will stagnate at a certain dose that we used. Second, we find some possible reasons for the collapse of the lymph system in HIV-1 infection — the loss of these restraining functions, and/or the genetic variability of the virus due to immune escape that enhances the virulence, which then bring the collapse of the immune system. In some conditions the system will produce a Hopf bifurcation. We also simulate the theoretical warrant of the feasibility of the combined chemotherapy strategies for the HIV-1 infected patient.

scholarly journals Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer

Metabolites ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 332
Author(s):  
Luis Gil-de-Gómez ◽  
David Balgoma ◽  
Olimpio Montero
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Immune Cells ◽  
Metabolic Profile ◽  
Tumor Antigens ◽  
Immune Escape ◽  
Immune Checkpoints ◽  
Cellular Processes ◽  
Immune Response To Cancer ◽  
Main Components

While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed.

scholarly journals Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore

2021 ◽  
pp. jclinpath-2020-207337
Author(s):  
Claudia Núñez-Torrón ◽  
Ana Ferrer-Gómez ◽  
Esther Moreno Moreno ◽  
Belen Pérez-Mies ◽  
Jesús Villarrubia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune System ◽  
Multiorgan Failure ◽  
Histological Findings ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Bone Marrow Tissue ◽  
Autopsy Findings ◽  
Specific Finding ◽  
Clinical Records

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Why Does SARS-CoV-2 Infection Induce Autoantibody Production?

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 380
Author(s):  
Ales Macela ◽  
Klara Kubelkova
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Host Cell ◽  
Critical Role ◽  
Cell Interaction ◽  
Immune Recognition ◽  
Autoantibody Production ◽  
Host Cell Interaction ◽  
Primary Virus

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient’s immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

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