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Updated: Feb 13, 2026

"Cell Surface Capture" Workflow for Label-Free Quantification of the Cell Surface Proteome
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Molecular pixelation of the CAR T cell surface proteome

Anthony Cesnik1,2, Oliver Takacsi-Nagy3,4, Trang Le1

  • 1Bioengineering Department, Stanford University, Stanford, CA, USA.

Biorxiv : the Preprint Server for Biology
|February 12, 2026
PubMed

Insights

CAR T cell exhaustion, a challenge in leukemia immunotherapy, can be identified by analyzing surface protein patterns. Molecular Pixelation reveals distinct proteomic signatures linked to chronic T cell stimulation, offering new insights for improving treatments.

Area of Science:

  • Immunology
  • Systems Biology
  • Cellular Proteomics

Background:

  • Chimeric antigen receptor (CAR) T cell immunotherapies show promise for B-cell acute lymphoblastic leukemia.
  • Patient non-responsiveness and reduced T cell function due to chronic stimulation limit CAR T cell efficacy.

Purpose of the Study:

  • To identify surface proteomic signatures of CAR T cell exhaustion using Molecular Pixelation.
  • To characterize topological differences in surface protein distribution associated with chronic T cell stimulation.

Main Methods:

  • Applied Molecular Pixelation to analyze 76 surface proteins on 8504 CAR T cells from three donors.
  • Compared CAR T cells subjected to acute (single) versus chronic (repeated) stimulation over two weeks.
  • Assessed protein abundance, polarization, and colocalization patterns at the single-cell level.

Main Results:

  • Surface protein abundances, polarizations, and colocalizations distinguished acutely from chronically stimulated CAR T cells.
  • Chronic stimulation led to increased protein polarization for most markers and disrupted adhesion signatures in the pSMAC.
  • Increased colocalization of CD37/CD82 was observed following chronic stimulation.

Conclusions:

  • Molecular Pixelation provides novel spatial signatures for proteomic polarization and colocalization on the cell surface.
  • These signatures offer new cell-state axes for understanding CAR T cell function and dysfunction in immunology and systems biology.
  • Findings may inform strategies to overcome T cell exhaustion and enhance immunotherapy effectiveness.

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