Prognostic role of S100A9 expression and CD8+ T cells infiltration and their interaction in RCC

Background: Renal carcinoma is common and highly malignant, it is not sensitive to chemo-radiotherapy, leading its poor progression. Currently, S100A9 was found to be associated with several human malignancies. The purpose of this study is to investigate S100A9 expression in renal cancer and explore its role in cancer progression and its interaction with CD8 ⁺ T cells. Methods: We analyzed the subcluster and differentiation states of monocytes and CD8 ⁺ T cells in RCC and their cellchart based on integrated scRNA-seq data. S100A9 expression and percentage of CD8 ⁺ T cell infiltration in RCC tissue samples from 79 patients were assessed by immunohistochemistry. Results: Monocytes were categorized into 5 clusters and S100A9 was mainly expressed by inflammatory cells on monocytes C1-1 in human RCC tissues, is a terminal status of monocytes and low expressed with immune checkpoints reported on monocytic cells. CD8 ⁺ T cells were defined into 5 clusters. Next, we identified strong interactions among Mono-C1-1 and ACT/CTL/EXT clusters with NAMPT-(IGTA5+IGTB1) and slightly interaction with VEGF pathway. Statistical analysis showed that a high percentage of S100A9 cells infiltration (> = 10%) in cancer tissues was positively correlated with poor prognosis. Further investigation found that S100A9 distribution in RCC was negatively related to CD8 ⁺ T cells infiltration. Conclusions: Our results showed S100A9 was mainly expressed in monocytes, while S100A9 in RCC is associated with poor prognosis and negatively related to CD8 ⁺ T cells infiltration by NAMPT-(IGTA5+IGTB1) and VEGF pathway.