The novel role of PTEN in governing the infiltration of neutrophils through the upregulation of CXC chemokines in renal cell carcinoma

In this study, we comprehensively integrate the single-cell RNA sequencing (sc-RNA-seq) data and bulk-RNA sequencing data, as well as genomic information of RCC. The frequently mutated tumor suppressor PTEN was found to be correlated with a suppressive tumor immune microenvironment. Depletion of PTEN in vitro dramatically increased the expression of multiple neutrophil chemokines, which were further confirmed both in vitro, clinical samples, and the publicly available databases. In keeping with that, the expression of neutrophil markers in RCC, validated by sc-RNA-seq, was significantly associated with a poor prognosis and response to the ICIs. In conclusion, our study provides insight into the association between genomic alternation and neutrophil infiltration, which indicated a poor prognosis and therapeutic response of ICIs in RCC. Molecular targeting of the PI3K-AKT-mTOR signaling pathway could have a synergistic effect in RCC patients with PTEN mutation.