Moving Immune Therapy Forward Targeting TME

2020 ◽  
Author(s):  
Kayla F Goliwas ◽  
Jessy S. Deshane ◽  
Craig A Elmets ◽  
Mohammad Athar
Keyword(s):  
Immune System ◽  
Targeted Therapies ◽  
Immune Therapy ◽  
Clinical Trial Design ◽  
Therapeutic Interventions ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Metabolic Plasticity ◽  
Cancer Pathogenesis ◽  
Immune Therapies

The host immune system shapes the fate of tumor progression. Hence, manipulating patients' immune system to activate host immune responses against cancer pathogenesis is a promising strategy to develop effective therapeutic interventions for metastatic and drug resistant cancers. Understanding the dynamic mechanisms within the tumor microenvironment (TME) that contribute to heterogeneity and metabolic plasticity is essential to enhance the patients' responsiveness to immune targeted therapies. Riera-Domingo et. al. describe the immune landscape within the TME, and highlight the significance of metabolic and hypoxic signatures that impact immune function and response to immunotherapy. Current literature in this field confirms that targeting tumor metabolism and the acidic microenvironment commonly associated with tumors may present as viable strategies to modulate the host immune system in favor of developing highly effective immune targeted therapies. However, development of better tools to understand tumor-immune interactions and identify mechanisms driving non-responders, more innovative clinical trial design, and new therapies will need to be identified to move the field forward. Personalized immune therapies incorporating metabolic and microbiome-based gene signatures to influence the therapeutic response and novel methods to generate immunologically "hot" tumors are at the forefront of immunotherapy currently. The combination of these approaches with clinically approved immunotherapies will also be valuable moving forward.

scholarly journals Cancer-Immunity Cycle and Therapeutic Interventions- Opportunities for Including Pet Dogs With Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Samantha K. Von Rueden ◽  
Timothy M. Fan
Keyword(s):  
Immune System ◽  
Animal Models ◽  
Tumor Formation ◽  
Therapeutic Interventions ◽  
Large Animal ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Large Animal Models ◽  
Cancer Immunity ◽  
Dynamic Series

The tumor-immune interplay represents a dynamic series of events executed by cellular and soluble participants that either promote or inhibit successful tumor formation and growth. Throughout a tumor’s development and progression, the host organism’s immune system reacts by generating anti-cancer defenses through various incremental and combinatorial mechanisms, and this reactive orchestration is termed the cancer-immunity cycle. Success or failure of the cancer-immunity cycle dictates the fate of both host and tumor as winner or loser. Insights into how the tumor and host immune system continuously adapt to each other throughout the lifecycle of the tumor is necessary to rationally develop new effective immunotherapies. Additionally, the evolving nature of the cancer-immunity cycle necessitates therapeutic agility, requiring real-time serial assessment of immunobiologic markers that permits tailoring of therapies to the everchanging tumor immune microenvironment. In order to accelerate advances in the field of immuno-oncology, this review summarizes the steps comprising the cancer-immunity cycle, and underscores key breakpoints in the cycle that either favor cancer regression or progression, as well as shaping of the tumor microenvironment and associated immune phenotypes. Furthermore, specific large animal models of spontaneous cancers that are deemed immunogenic will be reviewed and proposed as unique resources for validating investigational immunotherapeutic protocols that are informed by the cancer-immunity cycle. Collectively, this review will provide a progressive look into the dynamic interplay between tumor and host immune responses and raise awareness for how large animal models can be included for developing combinatorial and sequenced immunotherapies to maximizing favorable treatment outcomes.

An appraisal of survival strategies

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 575-577 ◽  
Author(s):  
N. A. Mitchison
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Survival Strategies ◽  
Host Immune System ◽  
Cellular Immunology ◽  
Host Immune Responses ◽  
Host Defence System ◽  
Bio Engineering

Only a few years ago parasite immunology looked an unattractive subject better left to the dogged specialists. Parasites and hosts had been playing chess together for a million years, and there seemed little prospect of perturbing matters in favour of the host immune system. All that has changed, for three reasons. Firstly, we have learned how to grow at least some parasites in vitro, and prospects of doing so with others are encouraging. Secondly, progress in cellular immunology has revealed the sort of loopholes in the host defence system which parasites are likely to exploit: we are learning the questions which matter about parasites as antigens. Thirdly, and most importantly, molecular genetics is being brought to bear on parasites: we can now see a real, though long-term, prospect of manufacturing practicable vaccines through bio-engineering, and more immediately it gives us the tools needed to probe the host immune responses in the form of cloned antigens.

scholarly journals Computational Model Informs Effective Control Interventions against Y. enterocolitica Co-Infection

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 431
Author(s):  
Reihaneh Mostolizadeh ◽  
Andreas Dräger
Keyword(s):  
Growth Rate ◽  
Immune System ◽  
Control Strategies ◽  
Model Organism ◽  
Effective Control ◽  
Host Immune System ◽  
Gastrointestinal Infections ◽  
Robert Koch Institute ◽  
Bacteria Growth ◽  
Host Immune Responses

The complex interplay between pathogens, host factors, and the integrity and composition of the endogenous microbiome determine the course and outcome of gastrointestinal infections. The model organism Yersinia entercolitica (Ye) is one of the five top frequent causes of bacterial gastroenteritis based on the Epidemiological Bulletin of the Robert Koch Institute (RKI), 10 September 2020. A fundamental challenge in predicting the course of an infection is to understand whether co-infection with two Yersinia strains, differing only in their capacity to resist killing by the host immune system, may decrease the overall virulence by competitive exclusion or increase it by acting cooperatively. Herein, we study the primary interactions among Ye, the host immune system and the microbiota, and their influence on Yersinia population dynamics. The employed model considers commensal bacterial in two host compartments (the intestinal mucosa the and lumen), the co-existence of wt and mut Yersinia strains, and the host immune responses. We determine four possible equilibria: disease-free, wt-free, mut-free, and co-existence of wt and mut in equilibrium. We also calculate the reproduction number for each strain as a threshold parameter to determine if the population may be eradicated or persist within the host. We conclude that the infection should disappear if the reproduction numbers for each strain fall below one, and the commensal bacteria growth rate exceeds the pathogen’s growth rate. These findings will help inform medical control strategies. The supplement includes the MATLAB source script, Maple workbook, and figures.

scholarly journals Targeting the Immune system and Epigenetic Landscape of Urological Tumors

2020 ◽  
Vol 21 (3) ◽  
pp. 829 ◽  
Author(s):  
João Lobo ◽  
Carmen Jerónimo ◽  
Rui Henrique
Keyword(s):  
Immune System ◽  
Targeted Therapies ◽  
Cancer Development ◽  
Supporting Evidence ◽  
Epigenetic Landscape ◽  
Immune System Function ◽  
Immune Therapies ◽  
Short And Long Term ◽  
Urological Tumors

In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

scholarly journals Balance and modulation of immunoediting for cancer treatment using synergistic nano-photo-immuno effects

Nanophotonics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3383-3389
Author(s):  
Ashley R. Hoover ◽  
Kaili Liu ◽  
Wei R. Chen
Keyword(s):  
Immune System ◽  
Cancer Treatment ◽  
Tumor Recurrence ◽  
Tumor Metastasis ◽  
Immune Therapy ◽  
Cancer Diagnostics ◽  
Treatment Modalities ◽  
Host Immune System ◽  
Profound Impact

Abstract Nanotechnology, photonics, and immunotherapy are far-reaching technologies with the potential to revolutionize the field of cancer diagnostics and therapeutics. While each technology has limitations in cancer treatment, they can be synergized to exert profound impact on the balance and modulation of immunoediting in tumor microenvironment (TME) and in the entire host immune system. We provide our perspectives on how nano-photo-immuno interactions can be used as an effective therapy, particularly when combined with other treatment modalities, such as checkpoint immune therapy, chemotherapy, and TME modulation, to provide a long-term, tumor-specific immunity against tumor metastasis and tumor recurrence.

Leishmanial selenoproteins and the host immune system: towards new therapeutic strategies?

2020 ◽  
Vol 114 (7) ◽  
pp. 541-544
Author(s):  
Sajad Rashidi ◽  
Kurosh Kalantar ◽  
Paul Nguewa ◽  
Gholamreza Hatam
Keyword(s):  
Immune System ◽  
Adverse Effects ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Leishmania Parasites

Abstract Optimum levels of selenoproteins are essential for starting and managing the host immune responses against pathogens. According to the expression of selenoproteins in Leishmania parasites, and since high levels of selenoproteins lead to adverse effects on immune cells and their functions, Leishmania parasites might then express selenoproteins such as selenomethionine in their structure and/or secretions able to challenge the host immune system. Finally, this adaptation may lead to evasion of the parasite from the host immune system. The expression of selenoproteins in Leishmania parasites might then induce the development of infection. We therefore suggest these molecules as new therapeutic candidates for the treatment of leishmaniasis.

scholarly journals Role of inflammatory markers in corona virus disease (COVID-19) patients: A review

2020 ◽  
Vol 245 (15) ◽  
pp. 1368-1375 ◽  
Author(s):  
Jyoti Upadhyay ◽  
Nidhi Tiwari ◽  
Mohd N Ansari
Keyword(s):  
Immune System ◽  
Critically Ill ◽  
Inflammatory Mediators ◽  
Critically Ill Patients ◽  
Virus Disease ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Host Immune System ◽  
Novel Virus

The whole world is locked down due to the outbreak of novel Coronavirus Disease 2019 (nCOVID-19). A novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus pandemic 2019. Investigating the role of inflammatory mediators and understanding the virology of nCOVID-19 virus help in designing a rational and effective therapy for this infection. This review provides an overview of the inflammatory mediators activated during nCOVID-19 infection and the pathophysiology of this viral infection. In this review, the authors have a detailed discussion about the types of viral strains of nCOVID-19, its mechanism of action, host immune response, and the dysregulation caused by the viruses in the host immune system causing disease progression. Understanding the role of inflammatory cytokines, chemokines, and clinical immunology will be the approach to find out the possible novel therapeutic interventions. Therapies involving regulation of immune responses help in inhibiting the various steps in the pathologies of infection. Also, updated knowledge regarding the dysregulation of immune system and disease outcome in critically ill patients serves as a precautionary measure in the development and evaluation of vaccine. Impact statement In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-α was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.

Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?

2019 ◽  
Vol 10 (1) ◽  
pp. 27-32 ◽  
Author(s):  
A.C. Wing ◽  
M. Kremenchutzky
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Current Knowledge ◽  
Clinical Trial Design ◽  
Host Immune System ◽  
Immune Mediated ◽  
Clinical Benefits ◽  
Multiple Sclerosis Patients ◽  
Faecal Microbiome ◽  
Vitamin Production

Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.

scholarly journals Evolution of animal immunity in the light of beneficial symbioses

2020 ◽  
Vol 375 (1808) ◽  
pp. 20190601 ◽  
Author(s):  
Nicole M. Gerardo ◽  
Kim L. Hoang ◽  
Kayla S. Stoy
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Host Immune System ◽  
System Evolution ◽  
Symbiotic Associations ◽  
Host Immune Responses ◽  
Immune System Evolution ◽  
System Maintenance ◽  
Key Aspects ◽  
Host Evolution

Immune system processes serve as the backbone of animal defences against pathogens and thus have evolved under strong selection and coevolutionary dynamics. Most microorganisms that animals encounter, however, are not harmful, and many are actually beneficial. Selection should act on hosts to maintain these associations while preventing exploitation of within-host resources. Here, we consider how several key aspects of beneficial symbiotic associations may shape host immune system evolution. When host immunity is used to regulate symbiont populations, there should be selection to evolve and maintain targeted immune responses that recognize symbionts and suppress but not eliminate symbiont populations. Associating with protective symbionts could relax selection on the maintenance of redundant host-derived immune responses. Alternatively, symbionts could facilitate the evolution of host immune responses if symbiont-conferred protection allows for persistence of host populations that can then adapt. The trajectory of immune system evolution will likely differ based on the type of immunity involved, the symbiont transmission mode and the costs and benefits of immune system function. Overall, the expected influence of beneficial symbiosis on immunity evolution depends on how the host immune system interacts with symbionts, with some interactions leading to constraints while others possibly relax selection on immune system maintenance. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

scholarly journals A Computational Model to Inform Effective Control Interventions against Yersinia enterocolitica Coinfection

2020 ◽  
Author(s):  
Reihaneh Mostolizadeh ◽  
Andreas Dräger
Keyword(s):  
Immune System ◽  
Control Strategies ◽  
Model Organism ◽  
Commensal Bacteria ◽  
Effective Control ◽  
Host Immune System ◽  
Wild Type ◽  
Gastrointestinal Infections ◽  
Robert Koch Institute ◽  
Host Immune Responses

The complex interplay among pathogens, host factors, and the integrity and composition of the endogenous microbiome determine the course and outcome of gastrointestinal infections. The model organism Yersinia entercolitica (Ye) is one of the five top frequent causes of bacterial gastroenteritis based on the Epidemiological Bulletin of the Robert Koch Institute (RKI) published on September 10, 2020. A fundamental challenge in predicting the course of an infection is to understand whether co-infection with two Yersinia strains differing only in their capacity to resist killing by the host immune system may decrease the overall virulence by competitive exclusion or increase it by acting cooperatively. Herein, we study the primary interactions among Ye, the host immune system and the microbiota, and their influence on Yersinia population dynamics. The employed model considers two host compartments, the intestinal mucosa and lumen, commensal bacteria, the co-existence of wild-type and mutant Yersinia strains, as well the host immune responses. We determine four possible equilibria: the disease-free, wild-type-free, mutant-free, and co-existence of wild-type and mutant equilibrium. We also calculate the reproduction number for each strain as a threshold parameter to determine if the population may either be eradicated or persist within the host. We conclude that the infection should disappear if the reproduction numbers for each strain fall below one, and the commensal bacteria’s growth rate exceeds the pathogens’ growth rates. These findings will help inform public health control strategies. The supplement includes MATLAB source script, Maple workbook, and figures.

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