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Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Predictive and prognostic markers
Analysis of Phenotypic and Molecular Variability of Memory-like NK Cells for Cancer Adoptive Cell Therapy Screening

Analysis of Phenotypic and Molecular Variability of Memory-like NK Cells for Cancer Adoptive Cell Therapy Screening

Rithvik V Turaga ^1,2,3, Seth R T Zima ^1,2,3, Ella P Peterson ^1,2,3, Amy K Erbe ^3,4, Matthew H Forsberg ⁵, Christian M Capitini ^3,5, Pippa F Cosper ^3,4, Paul M Sondel ^3,4,5, Jose M Ayuso ^1,2,3

Rithvik V Turaga ^1,2,3, Seth R T Zima ^1,2,3, Ella P Peterson ^1,2,3

¹Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, 1 S Park Street, Madison, WI 53715, USA.
²Department of Biomedical Engineering, College of Engineering, University of Wisconsin, 1550 Engineering Dr, Madison, WI 53706, USA.
³UW Carbone Cancer Center, 600 Highland Avenue, Madison, WI 53705, USA.
⁴Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
⁵Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.

⁰Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, 1 S Park Street, Madison, WI 53715, USA.

Cancers +

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July 29, 2025

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July 29, 2025

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View abstract on PubMed

Summary

This summary is machine-generated.

Memory-like natural killer (mlNK) cells show promise in cancer therapy due to improved persistence. This study reveals metabolic pathways linked to mlNK cell function, aiding in the selection of optimal cell products.

Area Of Science

Immunology
Cell Biology
Metabolic Engineering

Background

Adoptive cell therapies, including natural killer (NK) cells, are advancing cancer treatment.
Memory-like NK (mlNK) cells offer enhanced in vivo persistence, overcoming limitations of traditional NK cell therapy.
The quality and variability of mlNK cell products require further definition for clinical application.

Purpose Of The Study

To evaluate the heterogeneity of mlNK cells across functional and molecular domains.
To identify potential biomarkers for discriminating mlNK cell product quality.

Main Methods

Assessed mlNK cell cytotoxicity, cluster formation, motility, mitochondrial morphology, and gene expression.
Investigated the impact of metabolic pathways, specifically glycolysis and oxidative phosphorylation (OXPHOS), on mlNK cell function.

Main Results

Observed a correlation between gene expression related to glycolysis and NK cell functions like cytotoxicity and motility.
Blocking glycolysis or OXPHOS impaired mlNK cell functional responses, highlighting the critical role of cellular metabolism.

Conclusions

Metabolic pathways, particularly glycolysis, are crucial for mlNK cell function.
Identified potential predictive markers for selecting optimal mlNK cell products for adoptive cell therapy in cancer patients.

Keywords:

adoptive cell therapy head and neck squamous cell carcinoma immunotherapy memory-like natural killer cells natural killer cells phenotypic and molecular variability prediction

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