Signatures and Specificity of Tissue-Resident Lymphocytes Identified in Human Renal Peritumor and Tumor Tissue

Background Tissue-resident memory T (T-RM) cells are known to be important for the first line of defense in mucosa-associated tissues. However, the composition, localization, effector function, and specificity of T-RM cells in the human kidney and their relevance for renal pathology have not been investigated. Methods Lymphocytes derived from blood, renal peritumor samples, and tumor samples were phenotypically and functionally assessed by applying flow cytometry and highly advanced histology (multi-epitope ligand cartography) methods. Results CD69(+)CD103(+)CD8(+) T-RM cells in kidneys display an inflammatory profile reflected by enhanced IL-2, IL-17, and TNF alpha production, and their frequencies correlate with increasing age and kidney function. We further identified mucosa-associated invariant T and CD56(dim) and CD56(bright) natural killer cells likewise expressing CD69 and CD103, the latter significantly enriched in renal tumor tissues. CD8(+) T-RM cell frequencies were not elevated in kidney tumor tissue, but they coexpressed PD-1 and TOX and produced granzyme B. Tumor-derived CD8(+) T-RM cells from patients with metastases were functionally impaired. Both CD69(+)CD103(-)CD4(+) and CD69(+)CD103(-)CD8(+) T-RM cells form distinct clusters in tumor tissues in proximity to antigen-presenting cells. Finally, EBV, CMV, BKV, and influenza antigen-specific CD8(+) T cells were enriched in the effector memory T cell population in the kidney. Conclusions Our data provide an extensive overview of T-RM cells' phenotypes and functions in the human kidney for the first time, pointing toward their potential relevance in kidney transplantation and kidney disease.

Automated summary

The study identified inflammatory T-RM cells in the kidney, and found that CD8(+) T-RM cell frequencies correlate with age and kidney function. Additionally, natural killer cells expressing CD103 were enriched in renal tumor tissues.