Interleukin-15 cytokine checkpoints in natural killer cell anti-tumor immunity

Harrison Sudholz; Rebecca B Delconte; Nicholas D Huntington

doi:10.1016/j.coi.2023.102364

Interleukin-15 cytokine checkpoints in natural killer cell anti-tumor immunity

Curr Opin Immunol. 2023 Oct:84:102364. doi: 10.1016/j.coi.2023.102364. Epub 2023 Jul 12.

Authors

Harrison Sudholz¹, Rebecca B Delconte², Nicholas D Huntington³

Affiliations

¹ Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
² Immunology Program, Memorial Sloan Kettering Cancer Center, New York 10065, USA.
³ Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; oNKo-Innate Pty Ltd, Moonee Ponds, Victoria 3039, Australia. Electronic address: nicholas.huntington@monash.edu.

PMID: 37451129
DOI: 10.1016/j.coi.2023.102364

Abstract

Over recent years, the use of immune checkpoint inhibitors (ICI) has progressed to first and second-line treatments in several cancer types, transforming patient outcomes. While these treatments target T cell checkpoints, such as PD-1, LAG3 and CTLA-4, their efficacy can be compromised through adaptive resistance whereby tumors acquire mutations in genes regulating neoantigen presentation by MHC-I [93]. ICI-responsive tumor types such as advanced metastatic melanoma typically have a high mutational burden and immune infiltration; however, most patients still do not benefit from ICI monotherapy for a number of reasons [94]. This highlights the need for novel immunotherapy strategies that evoke the immune control of tumor cells with low neoantigen/MHC-I expression, overcome immune suppressive tumor microenvironments and promote tumor inflammation. In this regard, targeting natural killer (NK) cells may offer a solution to some of these bottlenecks.

Publication types

Review