Polyfunctional Cells are the Subsets with “Superpowers”: Part 1

Case Studies Part 1: Vaccines & Immunotherapy

Immune cells with high polyfunctionality are considered the ones with “superpowers,” which can be beneficial or detrimental in terms of their function. Most cells secrete one cytokine or possibly none, and occasionally they’ll start secreting multiple cytokines simultaneously. In many studies, IsoPlexis has observed that the presence of this unique subset of cells that are highly polyfunctional predict unique correlates such as anti-tumor activity, therapy persistence, etc. Dr. James R. Heath, President of Institute for Systems Biology, described this concept further:

“Being able to identify these cell subsets and characterize their function with single-cell proteomics can help researchers accelerate the development of immune therapies by giving them a previously unavailable way to identify the cell subsets with superpowers.”

These superhero cells play a critical role in the development of protective immunity in vaccines for infectious diseases. A malaria study by Zhou et al. published in Human Vaccines & Immunotherapeutics analyzed hepatic CD8+ T cells from mice immunized with a potential anti-malaria vaccine to identify distinct markers of polyfunctional response, which may correlate with anti-malaria protection.1 In the study, researchers used IsoPlexis’ single-cell proteomics to determine potential biomarkers for the efficacy of this vaccine. They analyzed samples from mice immunized with this anti-malaria vaccine, naïve mice, and mice who received irradiated non-infected mosquitoes’ salivary gland extracts (IrNSG). IsoPlexis’ single-cell secretome technology identified distinct markers of polyfunctional response in the mice given the novel vaccine. This polyfunctional CD8+ T cell subset, the highly functional superhero cells, from the vaccinated mice had a dominant profile secreting MIP-1α, RANTES, IFN-γ, and/or IL-17A and was predicted to be effective in eliciting protective immunity. “These results demonstrate that a group of polyfunctional hepatic CD8+ T cells, having both effector and chemoattractive functions at a single-cell level, may associate with anti-malaria immunity,”1 demonstrating the usefulness of IsoPlexis’ technology in aiding in the design of future vaccines. This subset of superhero cells with both effector and chemoattractive functions are considered superhero cells due to their increased polyfunctionality correlating to enhanced function.

Superhero cells also play a role in developing better immunotherapies for solid tumors. In a study published in Nature Communications, researchers Parisi et al. utilized IsoPlexis’ single-cell proteomics to understand the functional drivers of T cell persistence in response to a novel agonist in treating solid tumors.2 Mice treated with the novel agonist recruited the adoptively transferred cells into tumors, which were found to be highly polyfunctional and adept at simultaneously secreting both effector and chemoattractive cytokines. These cells, the superhero cells, identified by IsoPlexis’ technology, are predictive of an anti-tumor response. In a phase 1 clinical trial for melanoma patients, the circulating NK cell response and clear mechanistic upregulation of these polyfunctional cell subsets were found to be highly persistent and sustained a longer anti-tumor response than traditional ACT treatment with IL-2.2

This data suggests that polyfunctionality and functional phenotyping with IsoPlexis’ single-cell proteomics may provide a more comprehensive biomarker in solid tumor indications, accelerating insights in cancer immunology, and revealing predictive functional superhero cell subsets to accelerate the development of vaccines. Being able to identify polyfunctional cells or the cells with “superpowers” is imperative when creating immune therapies and vaccines. These cell subsets, when beneficial, can dictate immune persistence, anti-tumor activity, protective immunity, and more. Revealing the presence of these superhero or supervillain cells can help researchers create therapies that either home in on that function or combat it. In part two of this series, we will be covering the supervillain cells and how they contribute to disease progression.

To learn more about this superhero/supervillain cell concept, watch IsoPlexis’ webinar with Dr. Jim Heath of the Institute for Systems Biology here.


  1. Zhou J, et al. CD8+ T-cell mediated anti-malaria protection induced by malaria vaccines; assessment of hepatic CD8+ T cells by SCBC assay. Human Vaccines & Immunotherapeutics 13: 1625-1629, 2017.
  2. Parisi G, et al. Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist. Nature Communications 11: 660, 2020.
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