scholarly journals Systemic and mucosal immune profiling in asymptomatic and symptomatic SARS-CoV-2–infected individuals reveal unlinked immune signatures

2021 ◽  
Vol 7 (42) ◽  
Author(s):  
Supriya Ravichandran ◽  
Gabrielle Grubbs ◽  
Juanjie Tang ◽  
Youri Lee ◽  
Chang Huang ◽  
...  
Keyword(s):  
Immune Signatures ◽  
Immune Profiling

Deep Immune Profiling of Whole Blood to Identify Early Immune Signatures that Correlate to Patient Outcome after Major Trauma

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
April E. Mendoza ◽  
Susan Raju Paul ◽  
Majed El Hechi ◽  
Leon Naar ◽  
Charlie Nederpelt ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Whole Blood ◽  
Major Trauma ◽  
Immune Signatures ◽  
Immune Profiling

scholarly journals Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19

2020 ◽  
Vol 5 (51) ◽  
pp. eabd6197 ◽  
Author(s):  
Elizabeth R. Mann ◽  
Madhvi Menon ◽  
Sean Blandin Knight ◽  
Joanne E. Konkel ◽  
Christopher Jagger ◽  
...  
Keyword(s):  
Immune Response ◽  
Hospital Admission ◽  
Mononuclear Cells ◽  
Elevated Serum ◽  
Peripheral Blood Mononuclear ◽  
Immune Signatures ◽  
Enhanced Expression ◽  
The Uk ◽  
And Function ◽  
Immune Profiling

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.

scholarly journals Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures

2020 ◽  
Vol 14 (3) ◽  
pp. e0008112 ◽  
Author(s):  
Yujiao Zhao ◽  
Matthew Amodio ◽  
Brent Vander Wyk ◽  
Bram Gerritsen ◽  
Mahesh M. Kumar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Single Cell ◽  
Zika Virus ◽  
Innate Immune ◽  
Immune Signatures ◽  
Immune Profiling

scholarly journals Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002181
Author(s):  
Erin F Simonds ◽  
Edbert D Lu ◽  
Oscar Badillo ◽  
Shokoufeh Karimi ◽  
Eric V Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Prolonged Survival ◽  
Tumor Associated Macrophages ◽  
The Brain ◽  
Immune Profiling

BackgroundGlioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.MethodsWe used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.ResultsICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.ConclusionsOur data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.

Immune profiling of lupus miliaris disseminatus faciei and successful management with anti‐TNF therapy

2021 ◽  
Author(s):  
C. Alexanian ◽  
W. Liakos ◽  
A. Toussi ◽  
J. Kao ◽  
M.Y. Cheng ◽  
...  
Keyword(s):  
Successful Management ◽  
Immune Profiling

scholarly journals Characterizing the Tumor Immune Microenvironment with Tyramide-Based Multiplex Immunofluorescence

2020 ◽  
Vol 25 (4) ◽  
pp. 417-432
Author(s):  
Hidetoshi Mori ◽  
Jennifer Bolen ◽  
Louis Schuetter ◽  
Pierre Massion ◽  
Clifford C. Hoyt ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Multispectral Imaging ◽  
Imaging System ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Manual Processing ◽  
Cell Densities ◽  
Immune Profiling

AbstractMultiplex immunofluorescence (mIF) allows simultaneous antibody-based detection of multiple markers with a nuclear counterstain on a single tissue section. Recent studies have demonstrated that mIF is becoming an important tool for immune profiling the tumor microenvironment, further advancing our understanding of the interplay between cancer and the immune system, and identifying predictive biomarkers of response to immunotherapy. Expediting mIF discoveries is leading to improved diagnostic panels, whereas it is important that mIF protocols be standardized to facilitate their transition into clinical use. Manual processing of sections for mIF is time consuming and a potential source of variability across numerous samples. To increase reproducibility and throughput we demonstrate the use of an automated slide stainer for mIF incorporating tyramide signal amplification (TSA). We describe two panels aimed at characterizing the tumor immune microenvironment. Panel 1 included CD3, CD20, CD117, FOXP3, Ki67, pancytokeratins (CK), and DAPI, and Panel 2 included CD3, CD8, CD68, PD-1, PD-L1, CK, and DAPI. Primary antibodies were first tested by standard immunohistochemistry and single-plex IF, then multiplex panels were developed and images were obtained using a Vectra 3.0 multispectral imaging system. Various methods for image analysis (identifying cell types, determining cell densities, characterizing cell-cell associations) are outlined. These mIF protocols will be invaluable tools for immune profiling the tumor microenvironment.

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