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Applying single-cell highly multiplexed secretome proteomics to characterize immunotherapeutic products and predict
Weiming Ni1, Edward X Han1, Matthew Cyr1
1IsoPlexis Corporation, Branford, Connecticut, USA.
Insights
Single-cell secretome proteomics reveals immune cell heterogeneity. This technology identifies polyfunctional T cells, crucial for effective immunity against diseases and informing immunotherapy development.
Area of Science:
- Immunology
- Proteomics
- Biotechnology
Background:
- Immune cell populations, despite genetic identity, exhibit functional heterogeneity in protein secretion.
- Understanding this cellular heterogeneity is vital for advancing immunology and developing effective immunotherapies.
Purpose of the Study:
- To characterize immune cell heterogeneity using microfluidic chip-based single-cell highly multiplexed secretome proteomics.
- To identify polyfunctional T cell subsets and their cytokine signatures for improved immunotherapy strategies.
Main Methods:
- Utilized microfluidic chip technology for single-cell analysis.
- Applied highly multiplexed secretome proteomics to assess protein secretion profiles.
- Quantified simultaneous protein production at the single-cell level.
Main Results:
- Demonstrated that genetically identical immune cells display diverse functional and secretome profiles.
- Identified polyfunctional T cells (producing 2+ proteins) as key contributors to cellular immunity.
- Revealed distinct cytokine signatures associated with highly functional single-cell subsets.
Conclusions:
- Single-cell secretome proteomics is a powerful tool for dissecting immune cell functional heterogeneity.
- Identifying polyfunctional T cells and their signatures can guide the optimization of immunotherapeutic products.
- This approach aids in developing personalized immunotherapies for enhanced clinical outcomes.
Abstract:
Genetically and phenotypically identical immune cell populations can be highly heterogenous in terms of their immune functions and protein secretion profiles. The microfluidic chip-based single-cell highly multiplexed secretome proteomics enables characterization of cellular heterogeneity of immune responses at different cellular and molecular layers. Increasing evidence has demonstrated that polyfunctional T cells that simultaneously produce 2+ proteins per cell at the single-cell level are key effector cells that contribute to the development of potent and durable cellular immunity against pathogens and cancers. The functional proteomic technology offers a wide spectrum of cellular function assessment and can uniquely define highly polyfunctional cell subsets with cytokine signatures from live individual cells. This high-dimensional single-cell analysis provides deep dissection into functional heterogeneity and helps identify predictive biomarkers and potential correlates that are crucial for immunotherapeutic product design optimization and personalized immunotherapy development to achieve better clinical outcomes.
