56 THE SCIENTIST | the-scientist.com
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he immune system is a highly complex network of
molecules, cells, tissues, and organs that protect
the human body from foreign invaders and endog-
enous threats. The network is highly flexible in order to
respond to a broad range of threats, and much of this
flexibility is mediated by the diversity and plasticity of
its cells. Scientists have dedicated innumerable hours
towards studying and characterizing immune cells to
better understand how their properties affect health
and disease.
Much of what we know about immune cells comes from
studies founded on the use of techniques such as flow
cytometry to group and classify cells based on surface
markers. However, cellular surface markers generally do
not capture the depth of heterogeneity within a given cell
population, nor are they necessarily indicative of transcrip-
tional- or functional-level changes. These limitations are
particularly magnified when dealing with rare highly func-
tional cellular subsets, which scientists have revealed areinstrumental in driving key mechanisms affecting disease
susceptibility and treatment efficacy.Finding the Superheroes that Orchestrate
Immune Response
IsoPlexis’ functional proteomics platform was designed
to bridge this knowledge gap and has shed light on how
rare powerful subsets of cells orchestrate the immune
response in various therapies and diseases. IsoPlexis’
functional proteomics has been especially instrumental in
detecting and characterizing cellular polyfunctionality—the
ability for a single cell to secrete multiple cytokines. Single-
cell proteomics is a beneficial way to locate cell subsets
of interest for further investigation, helping characterize
cell-to-cell heterogeneity and identify key phenotypes that
play important roles in health and disease.
Highly polyfunctional cells are capable of secreting
multiple (two, three, four, five, or more) cytokines at the
same time. Researchers have linked these “superheroRevealing the Genetic Drivers of Superpowered
Cells with Duomic
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cells” to more potent and persistent immune responses
in a number of studies.1,2 Highly polyfunctional immune
cells are critical drivers of long-term responses in cell-
and immune-based therapeutic approaches, and their
presence is linked to—and may be predictive of—better
patient outcomes.1,2
However, despite the importance of cellular polyfunc-
tionality to immune system function in a therapeutic
context, there are significant gaps in scientists’ understand-
ing of the underlying mechanisms of polyfunctionality. In
particular, a knowledge gap exists between the observed
functional phenotypes and the underlying transcriptomic
changes. Integrating transcriptomics and proteomics at
the single-cell level is crucial for identifying the genetic
drivers of polyfunctionality. This information, in turn, can
potentially provide key insights into the genetic drivers of
the “superhero cells” orchestrating immune response.Enter Duomic
In continuing efforts to help scientists better establish
the connections between gene- and protein-level cellular
mechanics, IsoPlexis has created DuomicTM, a novel plat-
form that simultaneously captures transcriptomic and func-
tional proteomic data from the same single cell. DuomicTM
leverages IsoPlexis’ single-cell proteomics platform and
adds a new layer of transcriptomic-level information by con-
necting the genomic-level information back to each individ-
ual cell in each microchamber.
Researchers have used DuomicTM to better understand
the driving forces behind cellular polyfunctionality and the
creation of superhero cells. DuomicTM has been utilized to
identify the genomic drivers of highly polyfunctional sub-
sets of “superhero” T cells as well as establish unique gene
expression profiles, thereby uncovering the genes poten-
tially responsible for driving “superhero” polyfunctionality.^3
Similarly, researchers have also used DuomicTM to identifytwo distinct proteomic profiles when investigating individ-
ual melanoma cells: one with high heterogeneity and one
with low heterogeneity. They established that these subsets
presented unique gene expression profiles, offering insights
into the genetic drivers of functional heterogeneity.^4Accelerating into the Future
Linking transcriptomic and functional proteomic data from
the same cell allows researchers to establish a direct con-
nection, for the first time, between gene regulatory net-
works and the critical proteomic functions that they drive.
In particular, revealing the gene networks that regulate cel-
lular polyfunctionality offers valuable information on how
to promote polyfunctional cell generation to drive insights
for better therapies.References- B. Creelan et al., “Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant
metastatic lung cancer: a phase 1 trial,” Nat Med, 27, 1410-18, 2021. - J.Y. Spiegel et al., “CAR T cells with dual targeting of CD19 and CD22 in adult patients
with recurrent or refractory B cell malignancies: a phase 1 trial,” Nat Med, 27:1419-
31, 2021. - “Emerging standard single cell functional biomarkers of immune function and
potency, and Duomic, a novel simultaneous single cell transcriptomics and
functional proteomics platform to transform connected therapeutic biology”,
Presented at SITC, 2021 - “Highly multiplexed and simultaneous single cell transcriptomics and functional
proteomics to transform biology”, Presented at AGBT, 2021
For Research Use Only. Not for Use in Diagnostic Procedures. isoplexis.comIsoPlexis has created DuomicTM, a novel platform that simultaneously captures
transcriptomic and functional proteomic data from the same single cell.