Immune Exhaustion

Human and Mouse

For research in immuno-oncology, CAR-T cell therapy, infectious disease and drug development, the immune exhaustion panel is a multifaceted tool. Uncover the mechanisms behind T cell, B cell and NK cell exhaustion in diverse contexts, including cancer and infectious disease, with a 785 gene panel that gets you results fast. Characterize immune status, develop signatures for assessing the exhausted state, and identify novel therapeutic targets to prevent or reverse exhaustion- all with this curated panel from NanoString.


Benefits

01

Immune cell exhaustion is a growing focus of R&D efforts in immuno-oncology

02

Understanding how and when cells become exhausted is an important topic for research

03

Immune cell exhaustion is a dysfunctional state induced by chronic exposure to target antigen or inflammatory signals

04

Persistent viruses have been known to induce immune exhaustion



Details & Data

Characterizing Immune Status

Immune exhaustion results from a complex interplay between a cell and its environment. While checkpoint molecules and particular receptor signaling pathways within T cells, B cells and NK cells are strong signals regulating exhaustion, senescence, anergy and tolerance, these states are also influenced by cytokines and signaling from other cell types. Understanding immune exhaustion in the context of the overall immune cell status is an important assessment to make in order to determine the state of dysfunction, impact of therapeutics and the ability to intervene and reverse exhaustion.

States of Effector Dysfunction

Exhaustion is not the only context where an immune cell may lack effector function. As such, understanding the similarities and distinctions between states of dysfunction is key to understanding immune exhaustion.

Anergic

  • Suboptimal stimulation
  • Low proliferative capacity
  • None or low effector function

Exhausted

  • Persistent overstimulation
  • Low proliferative capacity
  • Low to moderate effector function
  • High expression of multiple inhibitory factors
  • Some exhausted cell subsets are reversible

Senescent

  • Repetitive stimulation
  • Low proliferative capacity
  • Low expression of inhibitory receptors
  • High effector function
  • Irreversible

Pathway Annotation to Functional Themes

Immune ActivationImmune SuppressionEpigeneticsImmune StatusImmune CheckpointsMetabolism & Microenvironment
Antigen PresentationIL-1 SignalingNK ReceptorsIL-10 SignalingEpigenetic ModificationAnergyCTLA4 SignalingFatty Acid Metabolism
AP-1 SignalingIL-2 SignalingOther Interleukin SignalingMyeloid Immune EvasionB Cell ExhaustionPD1 SignalingGlutamine Metabolism
ApoptosisIL-6 SignalingPI3K-AKT PathwayNotch SignalingNaiveT Cell Checkpoint SignalingGlycolysis and Glucose Import
B Cell MemoryIL-7 SignalingT Cell MemoryRAR SignalingNK ExhaustionHypoxia Response
BCR SignalingJAK/STAT SignalingTCR SignalingTGF-beta SignalingSenescence & QuiescencePPAR Signaling
Cell CycleMAPK SignalingTLR SignalingT Cell Exuastion
Chemokine SignalingmTOR SignalingTNF Signaling
CytotoxicityNF-k8 SignalingType I Interferon
DAP12 SignalingNK ActivityType II Interferon

Immune Checkpoint Coverage

The Immune Exhaustion Panel provides comprehensive coverage of the most relevant immune checkpoints that can potentially be used to modulate the dynamics of the immune response.

CD28ICOSLGLAG3TNFSF18ICOS
CD40PDCD1HAVCR2VSIRCD70
CD80TNFSF4TNFSF9CD27CD276
CD86CD274TNFRSF9CD40LGADORA2A
CTLA4PDCDILG2TNFRSF18TNFRSF4TIGIT

Viral Identification

Chronic infections caused by viruses and other pathogens can induce immune exhaustion. The Human Exhaustion Panel includes probes for Epstein-Barr virus (EBV) and Cytomegalovirus (CMB), and the Mouse Immune Exhaustion Panel includes probes for Lymphocytic Choriomeningitis (LCMV). The panel can be supplemented with up to 55 genes of your choice with a Panel Plus spike-in for studying exhaustion in the context of different types of infectious disease.

Immune Cell Profiling

Genes included in the Immune Exhaustion Panel provide unique cell profiling data to measure the relative abundance of 14 different immune cell types. The table below summarizes the genes included in each cell type signature, as qualified through biostatistical approaches and selected literature in the field of immunology.

Cell TypeHuman GenesCell Type# of Human Genes
B cellsBLK, CD19, FAM30A, FCRL2, MS4A1, PNOC, SPIB, TCL1A, TNFRSF17Mast CellsCPA3, HDC, MS4A2, TPSAB1/B2
CD45+ cellsPTPRCNK CD56dim cellsIL21R, KIR2DL3/4, KIR3DL1/2
CD8T cellsCD8A, CD8BNK cellsNCR1, XCL1/2
Cytotoxic cellsCTSW, GNLY, GZMA, GZMB, GZMH, KLRB1, KLRD1, KLRK1, NKG7, PRF1NeutrophilsCEACAM3, CSF3R, FCAR, FCGR3A/B, FPR1, S100A12, SIGLEC5
Dendritic cellsCCL13, CD209, HSD11B1T cellsCD3D, CD3E, CD3G, CD6, SH2D1A, TRAT1
Exhausted CD8 cellsCD244, EOMES, LAG3, PTGER4Th1 cellsTBX21
MacrophagesCD163, CD68, CD84, MS4A4ATregsFOXP3

Genes in panel

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Immune Exhaustion

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