Microbes as Master Immunomodulators: Immunopathology, Cancer and Personalized Immunotherapies

Lérias, Joana R.; Paraschoudi, Georgia; Sousa, Eric de; Martins, José Luı́s; Condeço, Carolina; Figueiredo, Nuno; Carvalho, Carlos; Dodoo, Ernest; Castillo-Martin, Mireia; Beltrán, Antonio; Ligeiro, Dário; Rao, Martin; Zumla, Alimuddin; Maeurer, Markus

doi:10.3389/fcell.2019.00362

Cited by 9 publications

(9 citation statements)

References 213 publications

(215 reference statements)

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“…Improved understanding of inflammatory and immune pathways governing protective or deleterious outcomes, provide novel opportunities to target specific pathways that mediate immune pathology (Figure 1). Advances in host-directed therapies (HDTs) now provide a range of options to enhance immune responses or reduce excessive inflammation A range of HDTS with different mechanisms of action are under consideration from cellular therapy with mesenchymal stromal (stem) cells (MSCs), biologics, and repurposed drugs with HDT potential (Lérias et al, 2020;Hui et al, 2020).…”

Section: Cellular Based Therapies To Reduce Excessive Inflammation and Immune-mediated Tissue Damagementioning

confidence: 99%

Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy — Achieving global consensus and visibility for cellular host-directed therapies

Zumla

Wang²,

Ippolito

et al. 2020

International Journal of Infectious Diseases

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As of May 17th 2020, the novel coronavirus disease 2019 (COVID-19) pandemic has caused 307,395 deaths worldwide, out of 3,917,366 cases reported to the World Health Organization. No specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and/or vaccines are found. In search of effective treatments, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical trials on a range of antiviral drug regimens and repurposed drugs in various combinations. A paradigm shift is underway from the current focus of drug development targeting the pathogen, to advancing cellular Host-Directed Therapies (HDTs) for tackling the aberrant host immune and inflammatory responses which underlie the pathogenesis of SARS-CoV-2 and high COVID-19 mortality rates. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. Currently, the ClinicalTrials.gov and the WHO Clinical Trials Registry Platform (WHO ICTRP) report a combined 28 trials exploring the potential of MSCs or their products for treatment of COVID-19. MSCs should also be trialed for treatment of other circulating WHO priority Blueprint pathogens such as MERS-CoV which causes upto 34% mortality rates. It's about time funding agencies invested more into development MSCs per se, and also for a range of other HDTs, in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 death rates and preventing long-term functional disability in those who survive disease.

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Section: Cellular Based Therapies To Reduce Excessive Inflammation and Immune-mediated Tissue Damagementioning

confidence: 99%

Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy — Achieving global consensus and visibility for cellular host-directed therapies

Zumla

Wang²,

Ippolito

et al. 2020

International Journal of Infectious Diseases

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“…In recent decades, the role of gut flora in the pathogenesis of asthma has been extensively studied [103][104][105]. The gut and lungs interact with each other through microbes and immune functions, achieve bidirectional regulation, and amplify immune signals.…”

Section: The Gut-lung Axis Theorymentioning

confidence: 99%

“…Disorders of the gut can be observed in lung diseases [105,[111][112][113][114]. Influenza virus can change the composition of intestinal flora and cause intestinal immune damage through Th17 cell mediation [115].…”

Section: The Gut-lung Axis Theorymentioning

confidence: 99%

The Protective Effects of Helicobacter pylori Infection on Allergic Asthma

Zuo¹,

Yue²,

Sun³

et al. 2020

Int Arch Allergy Immunol

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As an ancient Gram-negative bacterium, Helicobacter pylori has settled in human stomach. Eradicating H. pylori increases the morbidities of asthma and other allergic diseases. Therefore, H. pylori might play a protective role against asthma. The “disappearing microbiota” hypothesis suggests that the absence of certain types of the ancestral microbiota could change the development of immunology, metabolism, and cognitive ability in our early life, contributing to the development of some diseases. And the Hygiene Hypothesis links early environmental and microbial exposure to the prevalence of atopic allergies and asthma. Exposure to the environment and microbes can influence the growing immune system and protect subsequent immune-mediated diseases. H. pylori can inhibit allergic asthma by regulating the ratio of helper T cells 1/2 (Th1/Th2), Th17/regulatory T cells (Tregs), etc. H. pylori can also target dendritic cells to promote immune tolerance and enhance the protective effect on allergic asthma, and this effect relies on highly suppressed Tregs. The remote regulation of lung immune function by H. pylori is consistent with the gut-lung axis theory. Perhaps, H. pylori also protects against asthma by altering levels of stomach hormones, affecting the autonomic nervous system and lowering the expression of heat shock protein 70. Therapeutic products from H. pylori may be used to prevent and treat asthma. This paper reviews the possible protective influence of H. pylori on allergic asthma and the possible application of H. pylori in treating asthma.

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“…There is growing evidence that the immune system plays an important role in the development and progression of cancer [8,9]. The immune system has been reported to participate in different stages of cancer, and some immune checkpoint molecules (such as PD-1, PD-L1, and CTLA-4) are practicable targets of immunotherapy [10,11]. In addition, immune escape has also been con rmed to be a mechanistic marker for chemotherapy resistance in cancer [12].…”

Section: Introductionmentioning

confidence: 99%

Construction of a Prognostic Value Model in Papillary Renal Cell Carcinoma by Immune-Related Genes

Wang¹,

Gu²,

Ni³

2020

Preprint

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Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma, and the role of immune-related genes (IRGs) in tumorigenesis and metastasis is evident; its prognostic value in PRCC remains unclear. In this study, we downloaded the gene expression profiles and clinical data of patients with PRCC from The Cancer Genome Atlas (TCGA) database and obtained IRGs from the ImmPort database. A total of 371 differentially expressed IRGs (DEIRGs) were discovered between PRCC and normal kidney tissues. Prognostic DEIRGs (PDEIRGs) were identified by univariate Cox regression analysis. Then, we screened the four most representative PDEIRGs (IL13RA2, CCL19, BIRC5, and INHBE) and used them to construct a risk model to predict the prognosis of patients with PRCC. This model precisely stratified survival outcome and accurately identified mutation burden in PRCC. Thus, our results suggest that these four PDEIRGs are available prognostic predictors for PRCC. They could be used to assess the prognosis and to guide individualized treatments for patients with PRCC.

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Microbes as Master Immunomodulators: Immunopathology, Cancer and Personalized Immunotherapies

Cited by 9 publications

References 213 publications

Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy — Achieving global consensus and visibility for cellular host-directed therapies

Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy — Achieving global consensus and visibility for cellular host-directed therapies

The Protective Effects of <b><i>Helicobacter pylori</i></b> Infection on Allergic Asthma

Construction of a Prognostic Value Model in Papillary Renal Cell Carcinoma by Immune-Related Genes

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