IsoPlexis’ Functional Immune Landscaping Enables Critical Single-Cell Discoveries

  • IsoPlexis’ Single-Cell Secretome solutions for adaptive immune, innate immune, and inflammation provide functional immune landscaping for the identification of highly functional cell subsets driving immune response.
  • In a study published in Nature Communications, IsoPlexis’ functional immune landscaping identified an increase in T cell polyfunctionality, proliferation, homing, and persistence when adoptive cell transfer (ACT) was used with NKTR-214 rather than IL-2, leading to improved anti-tumor function in human and murine tumors.
  • In a forthcoming study, Su, et al. used IsoPlexis’ single-cell solutions for functional immune landscaping to identify immune biomarkers of COVID-19 and disease severity. The researchers found an upregulation of polyfunctional CD4+ and CD8+ T cells in the COVID-19 patients, as well as an upregulation of polyfunctional inflammatory monocytes. In the COVID-19 patients who were admitted to the ICU, these inflammatory monocytes were even further upregulated, which led to repressed T cell function and drove disease progression. Researchers thus used the drug Tocilizumab to treat patients’ inflammatory monocyte upregulation, which greatly improved outcomes.

Single-Cell Secretome Solution Stratifies Populations & Increases the Understanding and Efficacy of Immune Therapies

IsoPlexis has risen as the emerging standard for functional single-cell proteomics through its unique applications of functional immune landscaping, intracellular signaling omics, and high-plex automated immunoassays. Using IsoPlexis’ platform for this first application, functional immune landscaping, enables the identification of highly functional rare cell subsets that are referred to as “superpowered” for their ability to drive immune response. These highly functional cells can, for example, dictate disease progression (supervillains) or anti-tumor response (superheroes) across many kinds of complex diseases and disorders, including cancers, infectious diseases, and neurodegenerative disorders.

In a study published in Nature Communications, researchers Parisi, et al. utilized IsoPlexis’ Single-Cell Secretome technology to predict the anti-tumor response of a novel kinetically engineered IL-2 agonist, NKTR-214, with adoptive cell transfer (ACT) compared to the conventional IL-2 combination therapy. ACT with NKTR-214 resulted in increased proliferation, homing, and persistence of anti-tumor T cells in a murine melanoma model. This resulted in superior anti-tumor activity and the use of NKTR-214 led to an increase of polyfunctional T cells in murine spleens and tumors. ACT combined with NKTR-214 increased the polyfunctionality of T and NK cells in the peripheral blood of human patients. This enhanced polyfunctionality suggests that NKTR-214 has the potential to improve the anti-tumor effects of ACT in humans. This significant finding was enabled by IsoPlexis’ Single-Cell Secretome solution and novel polyfunctionality metric.

Functional Immune Landscaping Identifies Mechanistic Drivers and Treatment for COVID-19 Progression

In another study, researchers Su, et al. used IsoPlexis’ functional immune landscaping technology to identify biomarkers of COVID-19 disease progression by characterizing the immune response associated with COVID-19 infection and severity.

Led by Dr. James Heath of the Institute for Systems Biology (ISB) and the Seattle COVID Consortium, the team of researchers found a marked upregulation of polyfunctional CD4+ T cells, CD8+ T cells, and monocytes in COVID-19 patients compared to a control sample. However, while COVID-19 patients overall saw an upregulation in T cell polyfunctionality, the opposite was true for the subset of patients COVID-19 patients in the ICU. IsoPlexis’ single-cell proteomics showed a decrease in CD4+ and CD8+ T cell polyfunctionality in ICU COVID-19 patients, while monocyte polyfunctionality was significantly upregulated. This increase in functionally inflammatory monocytes led to T cell suppression, explaining the downregulation of T cells in the ICU sample.

IsoPlexis’ unique functional immune landscaping provided critical insights into the drivers of COVID-19 progression to help researchers choose the best option for effective treatment of severe COVID-19 cases. After finding that an increase in inflammatory monocyte cells drove disease progression, researchers identified an anti-inflammatory drug, Tocilizumab, which effectively reduced the inflammatory monocyte population and restored T cell functionality to improve outcomes for COVID-19 ICU patients and effectively eliminate infection.

IsoPlexis’ integrated platform provides unique metrics to accelerate the future of functional immune landscaping, enabling deeper insights into the drivers of complex diseases. Learn more about how IsoPlexis’ technology has allowed researchers to accelerate insights into COVID-19 treatment and vaccines in this webinar with Dr. James Heath.

References:

  1. Parisi, G., Saco, J.D., Salazar, F.B. et al.Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist. Nat Commun 11, 660 (2020).
  2. Su Y et al. Deep immunophenotyping of COVID-19 patients reveals early disease trajectories of severe infections. Pre-Print (2020)

 

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