# CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence

## TL;DR

This study shows that CSF2 promotes kidney cancer progression by changing neutrophils and activating autophagy, suggesting it could be a new treatment target.

## Contribution

The study reveals a novel mechanism by which CSF2 influences kidney cancer through PD-L1-mediated neutrophil polarization and autophagy activation.

## Key findings

- CSF2 is upregulated in kidney cancer tissues and linked to advanced stages and poor prognosis.
- CSF2 promotes tumor-supportive neutrophil polarization and enhances cancer cell proliferation and migration.
- CSF2 activates autophagy and upregulates PD-L1, effects reversed by autophagy inhibitors or PD-L1 knockout.

## Abstract

To investigate the role and underlying mechanisms of colony-stimulating factor 2 (CSF2) in the progression of kidney renal clear cell carcinoma (KIRC).

Transcriptomic and clinical data from The Cancer Genome Atlas were analyzed to assess the correlation between CSF2 expression, clinicopathological features, and patient prognosis. A neutrophil–tumor co-culture system was established to examine the effects of CSF2 on neutrophil polarization, tumor cell proliferation, migration, apoptosis, and autophagy. Protein expression was evaluated by flow cytometry, Western blot, and immunofluorescence. PD-L1 knockout and autophagy inhibitors (3-methyladenine and chloroquine) were used to explore regulatory mechanisms.

CSF2 expression was significantly upregulated in KIRC tissues and was positively associated with advanced tumor stage and poor prognosis. In vitro, CSF2 promoted neutrophil polarization toward the tumor-supportive N2 phenotype and enhanced the proliferation and migration of renal cancer cells while inhibiting apoptosis and reactive oxygen species production. Additionally, CSF2 upregulated PD-L1 expression in tumor cells and activated autophagy by increasing LC-3, Beclin1, and ATG7 levels. These effects were reversed by PD-L1 knockout or treatment with the autophagy inhibitor 3-methyladenine.

CSF2 promotes KIRC progression through PD-L1–mediated neutrophil polarization and autophagy activation, representing a potential therapeutic target.