Multi-Factor Clustering Incorporating Cell Motility Predicts T Cell Expansion Potential

Area of Science:

• Immunology
• Cell Biology
• Oncology

Background:

• T cell expansion is vital for cellular immunotherapy.
• T cell exhaustion and lack of proliferation complicate expansion in Chronic Lymphocytic Leukemia (CLL).

Purpose of the Study:

• To identify biomarkers and cell function measures predicting T cell proliferative potential in CLL.
• To improve prediction of T cell expansion outcomes and clinical prognosis in CLL.

Main Methods:

• Characterized CD4+/CD8+ T cells from healthy donors and CLL patients for proliferative potential and in vitro functions.
• Analyzed correlations between expansion, Rai stage, PD-1 expression, IL-2 secretion, and cell alignment on micropatterned features.
• Utilized functional readouts to group donors based on proliferative potential and motility.

Main Results:

• Single-factor analysis showed limited correlation between expansion and Rai stage or PD-1 expression.
• Incorporating IL-2 secretion and cell alignment identified three distinct donor groups with varying proliferative potential.
• These groups also displayed different motility characteristics, suggesting a link to proliferative capacity.

Conclusions:

• Novel functional readouts (IL-2 secretion, cell alignment) improve prediction of T cell expansion outcomes in CLL.
• These measures, combined with surface markers, offer enhanced prognostic value for CLL patients.
• Cellular motility may underlie observed differences in T cell proliferative potential in CLL.