CD161, a promising Immune Checkpoint, correlates with Patient Prognosis: A Pan-cancer Analysis

Background: CD161 is a promising immune checkpoint mainly expressed on natural killer (NK) cells and is essential for immunoregulatory functions. However, it remains obscure how CD161 correlates with immune infiltration and patient prognosis in pan-cancer. Methods: We employed HPA, TCGA, GTEx, TIMER2.0, and GEPIA2 databases as well as R language to analyze and visualize CD161 in cancers. Our twenty-four glioma samples were sequenced for validation. Results: Overall, CD161 was differentially expressed between most paired cancer and normal controls. Higher CD161 expression was associated with poorer overall survival (OS) in the TCGA LGG (HR = 2.18, 95%CI = 1.79-2.66, P < 0.001) and UVM (HR = 1.32, 95%CI = 1.05-1.65, P = 0.016) cohorts. In these two cancer types, CD161 was significantly correlated with expression levels of recognized immune checkpoints and the abundance of markers of specific immune subsets, including CD8+ T cells, dendric cells (DCs), M2 macrophages, and exhausted T cells (Texs). In addition, CD161 was involved in several immune pathways in LGG and UVM, highlighting its role in regulating immune processes in the context of oncology. Conclusions: CD161 is a potential prognostic biomarker and immunotherapy target in human cancers, especially brain lower grade gliomas.