Applying single‐cell highly multiplexed secretome proteomics to characterize immunotherapeutic products and predict clinical responses

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 highdimensional 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.

Single-Cell Analysis in Immuno-Oncology

“…When compared to flow cytometry, it was shown that chipbased cytometry offers a significantly increased sensitivity and a specificity of a similar level [60]. This approach may be also of a high diagnostic value since it can provide the detection and phenotyping of rare cell subsets in precious, small clinical samples [60,64,65]. IsoLight is also a new system that detects the secreted proteins from single cells based on single-cell barcode chip technology [66].…”