immune suppression
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Author(s):  
Beatrice Ragnoli ◽  
Patrizia Pochetti ◽  
Patrizia Pignatti ◽  
Mariangela Barbieri ◽  
Lucrezia Mondini ◽  
...  

Sleep health and its adaptation to individual and environmental factors are crucial to promote physical and mental well-being across animal species. In recent years, increasing evidence has been reported regarding the relationship between sleep and the immune system and how sleep disturbances may perturb the delicate balance with severe repercussions on health outcomes. For instance, experimental sleep deprivation studies in vivo have reported several major detrimental effects on immune health, including induced failure of host defense in rats and increased risk for metabolic syndrome (MetS) and immune suppression in humans. In addition, two novel risk factors for dysregulated metabolic physiology have recently been identified: sleep disruption and circadian misalignment. In light of these recent findings about the interplay between sleep and the immune system, in this review, we focus on the relationship between sleep deprivation and immunity against viruses, with a special interest in SARS-CoV-2 infection.


2022 ◽  
Author(s):  
Bo Wu ◽  
Qian Wang ◽  
Bowen Li ◽  
Xiaonan Wang ◽  
Xiaoni Zhan ◽  
...  

Abstract The tumor microenvironment controls the progression of tissue homeostasis leading to cancer.Accumulation of anti-inflammatory tumor-associated macrophages (TAM) has also been linked to worsening clinical outcomes as well as resistance to treatment in hepatocellular carcinoma(HCC).The current immune landscape for regulation by the presence of TAMs has been studies.It is known that LAMTOR1 undergoes phosphorylation to bind to Exo70 and other exocyst components and is enhancing the secretion of TGFB1 to facilitate the polarization of TAMs.The tumor-conditioned macrophages(TCM) numbers also correlated with enhanced number of regulatory T cells(Tregs) and decreased CD8+T cells in HCC.Mechanistically,TCM enhanced IL-10 production to diminished CD8+T cell activities.Our data demonstrate a novel immune therapeutic approach targeting TAMs immune suppression of T cell anti-tumor activities.


2022 ◽  
Vol 12 ◽  
Author(s):  
Paola Del Bianco ◽  
Laura Pinton ◽  
Sara Magri ◽  
Stefania Canè ◽  
Elena Masetto ◽  
...  

BackgroundAlthough gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome.MethodsPeripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters.ResultsChanges in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient’s outcome.ConclusionsThis work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use.


2022 ◽  
pp. 1-17
Author(s):  
Susannah G. Ellsworth ◽  
Stuart A. Grossman
Keyword(s):  

Author(s):  
John E. McGinniss ◽  
Eric Bernasconi ◽  
Homer L. Twigg ◽  
Alison Morris

The Analyst ◽  
2022 ◽  
Author(s):  
Xiaozhang Qu ◽  
Dan Sun ◽  
yuqi cheng ◽  
Jiafeng Wang ◽  
yan wang ◽  
...  

Programmed cell death ligand 1 (PD-L1) is considered a major immune checkpoint protein that mediates antitumor immune suppression and response. Effectively regulating PD-L1 expression and dynamic monitoring for immunotherapy has...


2021 ◽  
Vol 12 ◽  
Author(s):  
Tyler J. Loftus ◽  
Ricardo Ungaro ◽  
Marvin Dirain ◽  
Philip A. Efron ◽  
Monty B. Mazer ◽  
...  

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis via enzyme-linked immunospot assay. We found that circulating inflammatory markers were significantly higher early after bacterial sepsis compared with SARS-CoV-2. Both cohorts exhibited profound immune suppression through 21 days (suppressed HLA-DR expression, reduced mononuclear cell IFN-gamma production), and expanded numbers of myeloid-derived suppressor cells (MDSCs). In addition, MDSC expansion and ex vivo production of IFN-gamma and TNF-alpha were resolving over time in bacterial sepsis, whereas in SARS-CoV-2, immunosuppression and inflammation were accelerating. Despite less severe initial physiologic derangement, SARS-CoV-2 patients had similar incidence of secondary infections (23% vs 30%) as bacterial sepsis patients. Finally, COVID patients who developed secondary bacterial infections exhibited profound immunosuppression evident by elevated sPD-L1 and depressed HLA-DR. Although both bacterial sepsis and SARS-CoV-2 are associated with inflammation and immune suppression, their immune dyscrasia temporal patterns and clinical outcomes are different. SARS-CoV-2 patients had less severe early inflammation and organ dysfunction but had persistent inflammation and immunosuppression and suffered worse clinical outcomes, especially when SARS-CoV-2 infection was followed by secondary bacterial infection.


2021 ◽  
Vol 22 (24) ◽  
pp. 13175
Author(s):  
Sai Preethi Nakkina ◽  
Sarah B. Gitto ◽  
Jordan M. Beardsley ◽  
Veethika Pandey ◽  
Michael W. Rohr ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor five-year survival rate of less than 10%. Immune suppression along with chemoresistance are obstacles for PDAC therapeutic treatment. Innate immune cells, such as tumor-associated macrophages, are recruited to the inflammatory environment of PDAC and adversely suppress cytotoxic T lymphocytes. KRAS and MYC are important oncogenes associated with immune suppression and pose a challenge to successful therapies. Here, we targeted KRAS, through inhibition of downstream c-RAF with GW5074, and MYC expression via difluoromethylornithine (DFMO). DFMO alone and with GW5074 reduced in vitro PDAC cell viability. Both DFMO and GW5074 showed efficacy in reducing in vivo PDAC growth in an immunocompromised model. Results in immunocompetent syngeneic tumor-bearing mice showed that DFMO and combination treatment markedly decreased tumor size, but only DFMO increased survival in mice. To further investigate, immunohistochemical staining showed DFMO diminished MYC expression and increased tumor infiltration of macrophages, CD86+ cells, CD4+ and CD8+ T lymphocytes. GW5074 was not as effective in modulating the tumor infiltration of total CD3+ lymphocytes or tumor progression and maintained MYC expression. Collectively, this study highlights that in contrast to GW5074, the inhibition of MYC through DFMO may be an effective treatment modality to modulate PDAC immunosuppression.


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