The tumour microenvironment (TME) of
clear cell renal cell carcinoma (ccRCC) comprises multiple cell types, which promote tumour progression and modulate drug resistance and immune cell infiltrations via
ligand-receptor (LR) interactions. However, the interactions, expression patterns, and clinical relevance of LR in the TME in ccRCC are insufficiently characterised. This study characterises the complex composition of the TME in ccRCC by analysing the single-cell sequencing (
scRNA-seq) data of patients with ccRCC from the Gene expression omnibus database. On analysing the
scRNA-seq data combined with the
cancer genome atlas kidney renal clear cell
carcinoma (TCGA-KIRC) dataset, 46 LR-pairs were identified that were significantly correlated and had prognostic values. Furthermore, a new molecular subtyping model was proposed based on these 46 LR-pairs. Molecular subtyping was performed in two ccRCC cohorts, revealing significant differences in prognosis between the subtypes of the two ccRCC cohorts. Different molecular subtypes exhibited different clinicopathological features, mutational, pathway, and immune signatures. Finally, the LR.score model that was constructed using ten essential LR-pairs that were identified based on LASSO Cox regression analysis revealed that the model could accurately predict the prognosis of patients with ccRCC. In addition, the differential expression of ten LR-pairs in tumour and normal cell lines was identified. Further functional experiments showed that CX3CL1 can exert anti-tumorigenic role in ccRCC cell line. Altogether, the effects of
immunotherapy were connected to LR.scores, indicating that potential medications targeting these LR-pairs could contribute to the clinical benefit of
immunotherapy. Therefore, this study identifies LR-pairs that could be effective
biomarkers and predictors for molecular subtyping and
immunotherapy effects in ccRCC. Targeting LR-pairs provides a new direction for
immunotherapy regimens and prognostic evaluations in ccRCC.