Heterogeneity in NK Cell Subpopulations May Be Involved in Kidney Cancer Metastasis

Abstract

Although substantial progress has been made in the immunotherapy of kidney cancer, its efficacy varies from patient to patient, with many responding suboptimally or even developing metastases. Thus, research on the tumour immune microenvironment and immune cell heterogeneity is essential for kidney cancer treatment. In this study, natural killer (NK) cell populations were isolated using signature genes from the single-cell sequencing data of clear cell renal cell carcinoma (ccRCC) and normal kidney tissues and divided into three subpopulations according to the differences in gene expression profiles: NK(GZMH), NK(EGR1), and NK(CAPG). Gene set enrichment analysis revealed that NK(EGR1) and NK(CAPG) were closely related to tumour metastasis, as shown by kidney cancer metastasis to Hodgkin lymphoma, T-cell leukaemia, and Ki-1+ anaplastic large cell lymphoma. Thus, these two NK cell subpopulations are promising targets for inhibiting metastasis in ccRCC. Our findings revealed heterogeneity in the infiltrating NK cells of kidney cancer, which can serve as a reference for the mechanisms underlying metastasis in kidney cancer.