Single Cell-Pair Proteomics for Decoding Immune-Cancer Cell Interactions

Area of Science:

• Proteomics
• Cancer Research
• Microfluidics
• Immunology

Background:

• Cancer immunotherapy effectiveness is limited by tumor and immune response heterogeneity.
• Understanding single immune-cancer cell interactions is crucial for advancing cancer treatments.

Purpose of the Study:

• To develop and validate a microfluidic platform for single-cell proteomics profiling of immune-cancer cell interactions.
• To investigate the functional heterogeneity of natural killer (NK) cells interacting with K562 tumor cells.

Main Methods:

• A microfluidic platform was engineered for precise single-cell pairing, co-culture, and retrieval.
• Stable-isotope labeling and mass spectrometry were employed for proteomic analysis of individual cell pairs.
• Real-time microscopy monitored cell-pair interactions.

Main Results:

• Achieved a 95% success rate in single-cell pairing with minimal cell damage.
• Identified over 1000 protein groups per single cell pair.
• Discovered distinct functional sub-clusters within NK cells and identified potential biomarkers.

Conclusions:

• The developed platform offers a powerful tool for comprehensive immune-cancer cell interaction profiling.
• This approach facilitates the discovery of heterogeneous immune responses and prediction of biomarkers for cancer immunotherapy.