Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling

Eleni Syrimi; Naeem Khan; Paul Murray; Carrie Willcox; Tracey Haigh; Benjamin Willcox; Navta Masand; Claire Bowen; Danai B Dimakou; Jianmin Zuo; Sierra M Barone; Jonathan M Irish; Pamela Kearns; Graham S Taylor

doi:10.1016/j.isci.2024.110837

Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling

iScience. 2024 Aug 28;27(9):110837. doi: 10.1016/j.isci.2024.110837. eCollection 2024 Sep 20.

Authors

Eleni Syrimi¹, Naeem Khan^{1

2}, Paul Murray^{1

3}, Carrie Willcox¹, Tracey Haigh¹, Benjamin Willcox¹, Navta Masand¹, Claire Bowen⁴, Danai B Dimakou², Jianmin Zuo¹, Sierra M Barone^{5

6}, Jonathan M Irish^{5

6}, Pamela Kearns^{7

8}, Graham S Taylor¹

Affiliations

¹ Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
² Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
³ Health research Institute, University of Limerick, Limerick, Ireland.
⁴ Pathology department, Birmingham Children's Hospital, Birmingham, UK.
⁵ Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
⁶ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷ Cancer Research UK Clinical Trials Unit, National Institute for Health Research Birmingham Biomedical Research Centre, Birmingham, UK.
⁸ Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

Abstract

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naive pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumor sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor. Furthermore, the natural killer (NK) cells of pediatric cancer patients were less mature and less cytotoxic when tested in vitro. Culture of these NK cells with interleukin-2 restored their cytotoxicity. Collectively, our data show that NK cells in pediatric cancer patients are impaired through multiple mechanisms and identify rational strategies to restore their functionality.

Keywords: Cancer; Health sciences; Immunology; Pediatrics.