IsoPlexis_Apr2022_RT-UnderstandingTheRole - 8

ROUND T ABLE
GEN: How do these new proteomic insights
in superpower cells complement what you are
already working with? And how is it impacting
the genomic cell atlas?
POLLACK:
This is a great new technology. For the problems we're working
on right now, like CAR-T cells and checkpoint inhibitors,
there's been a big rush to look at the cells we already know are
important for these therapies and to see how the technology
can characterize them. But as we look at all the different situations
where in normal physiology cells are making proteins
and cytokines, we're going to be able to observe differences in
various disease and treatment settings. These efforts to characterize
the normal physiology in cancer and other diseases are
going to be important, and we may see important applications
in clinical situations that are not currently obvious. We know
that cytokine secretion, for example, is important in cancer
metastasis and how cancer cells that are circulating find out
where they're going to go. I'd like to see some of this work
done in that setting. That's exciting.
FAN:
I think that to some degree, this concept has been well
recognized in a very specific subdiscipline of immunology
research, and that's T cell polarization. We know for
decades that T cells polarize to Type 1 or Type 2 T cells, and
each type has a unique signature of cytokine secretion, like
interferon Gama and TNF alpha for Type 1 cells, and IL-4,
-5, and -13 for Type 2 cells. That's what we have known for
decades about T cell " polyfunctionality. " But I think this
concept is much broader and potentially ubiquitous, and not
limited to T cell polarization. For example, by assessing the
protein secretion profile of cancer cells during metastasis, we
may see different protein secretion profiles that can define
distinct phenotypes of cancer cells at different stages and
detect the ones that can secrete a range of proteins to break
down the extracellular matrix, migrate over a long distance,
attract blood vessel growth toward them, and then enter the
blood stream to initiate metastasis.
8 | GENengnews.com
We're very interested in senescence-associated secretory
phenotype (SASP), which is an important topic in aging
research but could be broadly implicated in many different
fields. For example, in cancer, SASP cells might generate
an inflammatory environment to predispose the tissue to
higher risk of neoplastic transformation, which means they
are going to develop cancer or an early stage of primary
tumor. Some stromal cells, once they become senescent, are
able to induce inflammation and may promote metastasis.
Different cell types when becoming senescent may have
totally different SASP signatures. How different senescent
cells impact the local tissue microenvironment remains
largely unknown. When you build a catalog of different
senescent cells, single-cell protein secretomics is one of the
most important tools to use to directly characterize different
senescent cells and the SASP signatures in order to build
an atlas of senescent cells across all different cell types and
different organs.
GEN: The articles recently published in Cell
looked at COVID-19 at different stages of disease-
one in the context of disease severity, and another
looking at early factors and mechanisms contributing
to long COVID, also known as PASC. What
are the similarities and differences in immune cell
function of patients among these stages?
HEATH:
We identified several factors that could predict the development
of long COVID in patients. Then we tried to understand
what long COVID meant in terms of immunological
relationships. That picture is one that's not going to be
painted well by any single analytic measure. We can see risk
factors for long COVID. You could even see them before
the patients got COVID and they have to do with autoantibodies
or certain co-morbidities. There are a few things that
get activated when you get COVID-19, such as reactivation
of latent viruses, and these things lead to ongoing immuno
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IsoPlexis_Apr2022_RT-UnderstandingTheRole

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