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Cell Granularity Reflects Immune Cell Function and Enables Selection of Lymphocytes with Superior Attributes for

Tongjin Wu1,2, Joel Heng Loong Tan3, Wei-Xiang Sin4

  • 1Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117583, Singapore.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 6, 2023
PubMed

Insights

Lymphocyte granularity, measured by side scatter (SSC), reveals cell state and function. Sorting cells by SSC effectively selects populations for enhanced immunotherapy applications.

Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Cellular morphology often correlates with cell function, following the
  • form follows function
  • principle.
  • Lymphocyte granularity, quantified by intrinsic side scatter (SSC), serves as a key indicator of cellular state and functional capacity.

Purpose of the Study:

  • To investigate the relationship between lymphocyte granularity (SSC) and cell function.
  • To determine if segregating lymphocytes based on SSC can yield populations with distinct and advantageous properties for immunotherapy.

Main Methods:

  • Utilized high-throughput cell sorting to isolate lymphocyte populations based on their side scatter (SSC) properties.
  • Characterized the functional attributes of SSC-high and SSC-low lymphocyte populations.
  • Evaluated CAR-T cells derived from SSC-low populations for immunotherapy potential.

Main Results:

  • Lymphocyte granularity increases from a naïve to a terminal effector state.
  • SSC-high lymphocytes mediate immediate effector functions.
  • SSC-low lymphocytes are highly proliferative and replenish the memory pool.
  • CAR-T cells from SSC-low populations exhibit enhanced naïve-like and stem cell memory phenotypes, improved CD4/CD8 ratios, and superior in vitro and in vivo target-killing capabilities.

Conclusions:

  • Lymphocyte segregation by biophysical properties (SSC) enables label-free selection of functionally distinct cell populations.
  • This approach offers a powerful strategy for optimizing cell-based immunotherapies, particularly CAR-T cell therapies.

Keywords:
T cellscell granularityimmunotherapylymphocyteside scatter

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