01.2018 | THE SCIENTIST 45U
nderstanding immune interactions are critical when it comes to immunotherapies
for all types of diseases. Immune interaction is driven by the way cells
communicate with each other. Immune cells use cytokines and chemokines
to communicate within the immune system. Either as part of normal cellular function,
or when challenged, immune cells release cytokines and chemokines which influence
cell proliferation, migration, identity, and more; however, “modeling an immunological
process can be challenging because the process may...contain multiple cell types, and
use multiple cytokines.”^1 One critical step in understanding this cell communication, and
thereby better understanding immune interaction is by identifying the cytokines secreted
by the immune cells. To help address this integral challenge, IsoPlexis’ technology offers
powerful, accessible, high-throughput functional proteomics to help identify the functional
mechanisms and drivers of cancer and infectious diseases.
In infectious disease, it’s crucial to identify protective T cell response for vaccine
development, establish cellular immune monitoring for protective response early in patients,
and cellular prediction and cytokine level monitoring for toxicities related to cytokine storm.
IsoPlexis’ IsoLight® system provides a solution for the single-cell and accelerated population
level functional proteomics required to overcome these challenges. By detecting the range
of cellular proteomics involved in the immune response, researchers can better understand
functional mechanisms for the development of vaccines and novel therapies for cancer and
infectious diseases.
Functional Cellular Proteomics Powered by the IsoPlexis Platform
The IsoLight system runs both the IsoCode and CodePlex chips. IsoCode chips capture
individual cells using microfluidic microchambers. The cytokines secreted by a given
cell are then captured by an antibody barcode, creating a single cell cytokine profile
that scientists can use to identify functional correlates of persistence, resistance, and
suppression. Additionally, run on the same system, CodePlex chips allow for accelerated
insight, measuring the cytokines present within a sample using a rapid automated method
with small sample volumes and only five minutes of hands-on time. Both IsoCode and
CodePlex chips target over 30 cytokines in a highly multiplexed manner in both single cells
and population serum samples, respectively.
The IsoLight is a hub for comprehensive functional profiling of each cell type across a
large assay menu of single-cell and population proteomic chips across many high impact
applications. It fills the gap missing from current technologies of being able to look at the
extracellular phenotype of each cell, helping scientists directly identify the functional drivers
of persistence, resistance, and suppression, as well as cytokine storm and toxicity.
From infectious disease to cancer immunology, CodePlex can identify immune
signatures in a completely automated highly multiplexed fashion with small sample volume
and only five minutes of hands-on time. The Human Innate Immune panel is coming soon.
The currently available CodePlex panels are:
- Panel Menu:
Granzyme B, IFN-γ, MIP-1α, Perforin, TNF-α, TNF-β, GM-CSF, IL-2, IL-5, IL-7, IL-8,
IL-9, IL-12, IL-15, IL-21, CCL11, IP-10, MIP-1β, RANTES, IL-4, IL-10, IL-13, IL-22,
TGF-β1, sCD137, sCD40L, IL-1β, IL-6, IL-17A, IL-17F, MCP-1, MCP-4, IL-18, TGF-α,
BCA-1, IL-12-p40, MIF, EGF, PDGF-BB, VEGF- Human Adaptive Immune:
IL-17A, TGF-β1, MIP-1α, IL-9, MIP-1β, IL-6, IL-7, IL-8, IFN-γ, IP-10, GM-CSF, IL-4, IL-5, IL-10,
TNF-α, MCP-1, IL-13, IL-2, Perforin, sCD40L, sCD137, TNF-β, Granzyme B, IL- - Human Cytokine Storm:
IL-1β, IL-2, IL-4, IL-6, IL-7, IL-10, IL-12, IL-13, IL-17, MCP-1, GM-CSF, MIP-1α, TNF-α, IFN-γ
- Human Adaptive Immune:
Finding What Makes Cancer Cells Move
Cytokines are playing a critical role from infectious disease to cancer immunology. The
IsoPlexis platform has proven instrumental in helping researchers establish a link between
cytokine activity and cancer cell behavior. Published inNature Communications, Jayatilaka,
et al.^2 at Johns Hopkins University School of Medicine describe how they used functional
cellular proteomics to explore cancer cell metastasis.
To identify the functional drivers promoting migration, Jayatilaka, et al. cultured cancer
cells within 3D collagen matrices at high and low densities. They found that cells moved
much faster at high densities. Transferring culture medium conditioned by high-density
cells into low-density matrices recapitulated this phenomenon in the absence of increased
physical density.
The team then identified the responsible factors by characterizing the secretomic
profiles of sarcoma and carcinoma cells grown at high and low densities and comparing
them. To do this, they determined the concentrations of 24 soluble molecules using
IsoPlexis’ highly multiplexed CodePlex technology. They discovered that IL-6 and IL-8 were
both secreted in high concentrations that increased in abundance as cell density increased.
IL-6 and IL-8 were the only assayed secreted proteins with elevated concentrations at higher
cell densities; the researchers saw no change in growth factors such as FGF and VEGF,
chemokines such as RANTES and MIP1α, or other pro-inflammatory cytokines such as IFNγ
and TNFα. Jayatilaka, et al. further discovered that the effects of IL-6 and IL-8 occurred only
when both interleukins were active. The presence of either IL-6 or IL-8 alone failed to elicit
any increase in cell velocity and blocking either IL-6 or IL-8 function using RNA interference
or receptor antagonists eliminated pro-migratory effects.New Understandings, New Therapeutic Potential
Functional cellular proteomics helps scientists better understand cancer cell behavior in
order to identify potential treatment approaches as well as understand immune interactions
to better treat cancer and infectious diseases. Using IsoPlexis’ platform, Jayatilaka, et al.
discovered a novel synergistic paracrine signaling pathway centered around IL-6 and IL-
secretion that plays a critical role in cancer cell migration. This pathway may represent a
new therapeutic target for decreasing the metastatic capabilities of cancer cells and thereby
improving patient outcomes.References- H. Daneshpour et al., “Modeling cell–cell communication for immune systems across space
and time,” Curr Opin Syst Biol, 18: 44-52, 2019. - H. Jayatilaka et al., “Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy
to inhibit tumour cell migration,” Nat Commun, 8:15584, 2017.
Highly Multiplexed Proteomics from IsoPlexis
®
is AcceleratingInsights from Infectious Diseases to Cancer Immunology
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