# Distinct Tumor-Associated Macrophage Signatures Shape the Immune Microenvironment and Patient Prognosis in Renal Cell Carcinoma

## TL;DR

This study shows that different types of immune cells called tumor-associated macrophages affect kidney cancer progression and patient survival, offering new ways to predict outcomes and improve treatment.

## Contribution

The study introduces eight distinct TAM signatures and a 27-gene TAM risk model for predicting patient survival in renal cell carcinoma.

## Key findings

- Specific TAM signature gene expressions are significant prognostic markers for RCC patient survival.
- A 27-gene TAM risk model successfully stratifies RCC patients into risk categories with distinct survival outcomes.
- TAM signatures correlate with macrophage infiltration and modulate the tumor immune microenvironment in RCC.

## Abstract

Renal cell carcinoma (RCC) accounts for 90% of adult renal cancer cases and is characterized by significant heterogeneity within its tumor microenvironment. This study tests the hypothesis that tumor-associated macrophages (TAMs) influence RCC progression and patient response to treatment by investigating the prognostic implications of TAM signatures. Utilizing independent single-cell RNA sequencing data from RCC patients, we developed eight distinct TAM signatures reflective of TAM presence. A LASSO Cox regression model was constructed to predict survival outcomes, evaluated using the TCGA dataset, and validated across independent RCC cohorts. Model performance was assessed through Kaplan–Meier survival plots, receiver operating characteristic (ROC) curves, and principal component analysis. Survival analysis demonstrated that specific TAM signature gene expressions serve as significant prognostic markers, identifying TAM signatures positively correlated with patient survival and macrophage infiltration. A 27-gene TAM risk model was established, successfully stratifying patients into risk categories, with low-risk patients showing improved overall survival. These findings provide insights into the role of TAMs in modulating the RCC tumor immune microenvironment and their impact on patient prognosis, suggesting that TAM-based signatures may serve as useful prognostic markers and potential targets to enhance RCC treatment strategies.