immune biomarkers
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Author(s):  
U. Sivagnanalingam ◽  
P.L. Beatty ◽  
C. Jacqueline ◽  
M. Dracz ◽  
J. Adams-Haduch ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Gang Xu ◽  
Furong Qi ◽  
Haiyan Wang ◽  
Yu Liu ◽  
Xin Wang ◽  
...  

COVID-19 patients show heterogeneous and dynamic immune features which determine the clinical outcome. Here, we built a single-cell RNA sequencing (scRNA-seq) dataset for dissecting these complicated immune responses through a longitudinal survey of COVID-19 patients with various categories of outcomes. The data reveals a highly fluctuating peripheral immune landscape in severe COVID-19, whereas the one in asymptomatic/mild COVID-19 is relatively steady. Then, the perturbed immune landscape in peripheral blood returned to normal state in those recovered from severe COVID-19. Importantly, the imbalance of the excessively strong innate immune response and delayed adaptive immunity in the early stage of viral infection accelerates the progression of the disease, indicated by a transient strong IFN response and weak T/B-cell specific response. The proportion of abnormal monocytes appeared early and rose further throughout the severe disease. Our data indicate that a dynamic immune landscape is associated with the progression and recovery of severe COVID-19, and have provided multiple immune biomarkers for early warning of severe COVID-19.


Author(s):  
Yonina R. Murciano-Goroff ◽  
Terry Pak ◽  
Sebastian Mondaca ◽  
Jessica R. Flynn ◽  
Joseph Montecalvo ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Nick van Dijk ◽  
Alberto Gil-Jimenez ◽  
Karina Silina ◽  
Maurits L. van Montfoort ◽  
Sarah Einerhand ◽  
...  

Candidate immune biomarkers have been proposed for predicting response to immunotherapy in urothelial cancer (UC). Yet, these biomarkers are imperfect and lack predictive power. A comprehensive overview of the tumor immune contexture, including Tertiary Lymphoid structures (TLS), is needed to better understand the immunotherapy response in UC. We analyzed tumor sections by quantitative multiplex immunofluorescence to characterize immune cell subsets in various tumor compartments in tumors without pretreatment and tumors exposed to preoperative anti-PD1/CTLA-4 checkpoint inhibitors (NABUCCO trial). Pronounced immune cell presence was found in UC invasive margins compared to tumor and stroma regions. CD8+PD1+ T-cells were present in UC, particularly following immunotherapy. The cellular composition of TLS was assessed by multiplex immunofluorescence (CD3, CD8, FoxP3, CD68, CD20, PanCK, DAPI) to explore specific TLS clusters based on varying immune subset densities. Using a k-means clustering algorithm, we found five distinct cellular composition clusters. Tumors unresponsive to anti-PD-1/CTLA-4 immunotherapy showed enrichment of a FoxP3+ T-cell-low TLS cluster after treatment. Additionally, cluster 5 (macrophage low) TLS were significantly higher after pre-operative immunotherapy, compared to untreated tumors. We also compared the immune cell composition and maturation stages between superficial (submucosal) and deeper TLS, revealing that superficial TLS had more pronounced T-helper cells and enrichment of early TLS than TLS located in deeper tissue. Furthermore, superficial TLS displayed a lower fraction of secondary follicle like TLS than deeper TLS. Taken together, our results provide a detailed quantitative overview of the tumor immune landscape in UC, which can provide a basis for further studies.


2021 ◽  
Vol 10 (24) ◽  
pp. 5815
Author(s):  
Ivo Udovicic ◽  
Ivan Stanojevic ◽  
Dragan Djordjevic ◽  
Snjezana Zeba ◽  
Goran Rondovic ◽  
...  

Immune cells and mediators play a crucial role in the critical care setting but are understudied. This review explores the concept of sepsis and/or injury-induced immunosuppression and immuno-inflammatory response in COVID-19 and reiterates the need for more accurate functional immunomonitoring of monocyte and neutrophil function in these critically ill patients. in addition, the feasibility of circulating and cell-surface immune biomarkers as predictors of infection and/or outcome in critically ill patients is explored. It is clear that, for critically ill, one size does not fit all and that immune phenotyping of critically ill patients may allow the development of a more personalized approach with tailored immunotherapy for the specific patient. In addition, at this point in time, caution is advised regarding the quality of evidence of some COVID-19 studies in the literature.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jakob Hjorth von Stemann ◽  
Lars Klingen Gjærde ◽  
Eva Kannik Haastrup ◽  
Lia Minculescu ◽  
Patrick Terrence Brooks ◽  
...  

AbstractCytokine-specific autoantibodies (c-aAbs) represent an emerging field in endogenous immunodeficiencies, and the immunomodulatory potential of c-aAbs is now well documented. Here, we investigated the hypothesis that c-aAbs affects inflammatory, immunoregulatory and injury-related processes and hence the clinical outcome of haematopoietic stem cell transplantation (HSCT). C-aAbs against IL-1α, IL-6, IL-10, IFNα, IFNγ and GM-CSF were measured in 131 HSCT recipients before and after (days + 7, + 14, + 28) HSCT and tested for associations with 33 different plasma biomarkers, leukocyte subsets, platelets and clinical outcomes, including engraftment, GvHD and infections. We found that c-aAb levels were stable over the course of HSCT, including at high titres, with few individuals seeming to acquire high-titre levels of c-aAbs. Both patients with stable and those with acquired high-titre c-aAb levels displayed significant differences in biomarker concentrations and blood cell counts pre-HSCT and at day 28, and the trajectories of these variables varied over the course of HSCT. No clinical outcomes were associated with high-titre c-aAbs. In this first study of c-aAbs in HSCT patients, we demonstrated that high-titre levels of c-aAb may both persist and emerge in patients over the course of HSCT and may be associated with altered immune biomarkers and cell profiles.


2021 ◽  
Vol 99 (12) ◽  
Author(s):  
Yanshuo S Li ◽  
Joice V San Andres ◽  
Melanie D Trenhaile-Grannemann ◽  
Dana M van Sambeek ◽  
Kelly C Moore ◽  
...  

Abstract Addition of pre- and probiotics may confer growth and health benefits when added to the diet of pigs. To determine the effects of feeding mannan oligosaccharide (MOS) and Lactobacillus mucosae (LM) as prebiotic and probiotic sources in weanling pigs under immune challenge, 96 weaned pigs were randomly allotted to 16 experimental pens within a 2 × 2 factorial arrangement of treatments. Control diets with or without 0.1% yeast-derived MOS were randomly assigned to pens and 109 cfu/pig LM broth or a control broth were top-dressed daily. Pigs were fed one of four dietary treatments (control, MOS, LM, and MOS+LM) in Phases I and II (days 0 to 7 and days 7 to 21 postweaning, respectively) and a common diet during Phase III (days 21 to 35 postweaning). On day 14, all pigs were challenged with 100 µg/kg body weight (BW) Escherichia coli lipopolysaccharide (LPS) via intraperitonial injection. Feed disappearance and pig BW were measured weekly. Blood and fecal samples were collected weekly, and additional blood samples were collected on days 1 and 3 post-LPS challenge. On days 15 and 21, one pig per pen was euthanized for collection of ileal mucosa and duodenal and ileal tissue samples. From days 0 to 14, feeding LM decreased gain-to-feed ratio (G:F; P < 0.05). An interaction between LM and MOS was observed for G:F on days 14 to 21 (P < 0.05); G:F in LM (715 g/kg) was greater compared with MOS+LM (P < 0.05; 600 g/kg) and control (P < 0.10; 615 g/kg), but was not different (P > 0.10) from MOS (674 g/kg). After pigs were fed a common diet (days 21 to 35), G:F was decreased (P < 0.05) in the LM treatment groups. Pigs fed diets that included MOS had increased serum immunoglobulin (Ig) G on days 1 and 3 post-LPS challenge and 2 wk after removal of treatments (P < 0.05) and on days 14 and 21 postweaning (P < 0.10) compared with pigs fed diets without MOS. On day 15, mucosal immunoglobulin G was increased (P < 0.05) in control vs. MOS and LM groups. Circulating IL-1β in control and MOS+LM pigs increased (P < 0.05) on day 1 post-LPS challenge but did not change (P > 0.10) in MOS and LM groups. On day 15, pigs fed LM had decreased (P < 0.05) ileal crypt depth compared with pigs fed the control diet. On day 21, fecal propionate and butyrate tended to be lower (P < 0.10) in pigs fed MOS vs. control and MOS+LM diet. These preliminary findings suggest that feeding LM alone improved feed efficiency and ileal morphological structure during the first week of LPS challenge; additionally, feeding LM and MOS may have beneficial effects relative to immune biomarkers.


2021 ◽  
Vol 9 (12) ◽  
pp. e003585
Author(s):  
Amrit S Gonugunta ◽  
Mitchell S von Itzstein ◽  
Hong Mu-Mosley ◽  
Farjana Fattah ◽  
J David Farrar ◽  
...  

Immune-related adverse events (irAE) may affect almost any organ system and occur at any point during treatment with immune checkpoint inhibitors (ICI). We present a patient with advanced lung cancer receiving antiprogrammed death 1 checkpoint inhibitor who developed a delayed-onset visual irAE treated with corticosteroids. Through assessment of longitudinal biospecimens, we analyzed serial autoantibodies, cytokines, and cellular populations. Months after ICI initiation and preceding clinical toxicity, the patient developed broad increases in cytokines (most notably interleukin-6 (IL-6), interferon-γ (IFNγ), C-X-C motif chemokine ligand 2 (CXCL2), and C–C motif chemokine ligand 17 (CCL17)), autoantibodies (including anti-angiotensin receptor, α-actin, and amyloid), CD8 T cells, and plasmablasts. Such changes were not observed in healthy controls and ICI-treated patients without irAE. Administration of corticosteroids resulted in immediate and profound decreases in cytokines, autoantibodies, and inflammatory cells. This case highlights the potential for late-onset changes in humoral and cellular immunity in patients receiving ICI. It also demonstrates the biologic effects of corticosteroids on these parameters. Application of humoral and cellular immune biomarkers across ICI populations may inform toxicity monitoring and management.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Wang ◽  
Huaicheng Tan ◽  
Ting Yu ◽  
Xiaoxuan Chen ◽  
Fangqi Jing ◽  
...  

mRNA vaccines against cancer have advantages in safety, improved therapeutic efficacy, and large-scale production. Therefore, our purpose is to identify immune biomarkers and to analyze immune status for developing mRNA vaccines and selecting appropriate patients for vaccination. We downloaded clinical information and RNA-seq data of 494 LUAD patients from TCGA. LUAD mutational information was hierarchically clustered by NMF package (Version 0.23.0). DeconstructSigs package (Version 1.8.0) and NMF consistency clustering were used to identify mutation signatures. Maftools package (Version 2.6.05) was used to select LUAD-related immune biomarkers. TIMER was used to discuss the correlation between genetic mutations and cellular components. Unsupervised clustering Pam method was used to identify LUAD immune subtypes. Log-rank test and univariate/multivariate cox regression were used to predict the prognosis of immune subtypes. Dimensionality reduction analysis was dedicated to the description of LUAD immune landscape. LUAD patients are classified into four signatures: T >C, APOBEC mutation, age, and tobacco. Then, GPRIN1, MYRF, PLXNB2, SLC9A4, TRIM29, UBA6, and XDH are potential LUAD-related immune biomarker candidates to activate the immune response. Next, we clustered five LUAD-related immune subtypes (IS1–IS5) by prognostic prediction. IS3 showed prolonged survival. The reliability of our five immune subtypes was validated by Thorsson’s results. IS2 and IS4 patients had high tumor mutation burden and large number of somatic mutations. Besides, we identified that immune subtypes of cold immunity (patients with IS2 and IS4) are ideal mRNA vaccination recipients. Finally, LUAD immune landscape revealed immune cells and prognostic conditions, which provides important information to select patients for vaccination. GPRIN1, MYRF, PLXNB2, SLC9A4, TRIM29, UBA6, and XDH are potential LUAD-related immune biomarker candidates to activate the immune response. Patients with IS2 and IS4 might potentially be immunization-sensitive patients for vaccination.


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