High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma

Xingchao Wang; Jianfeng Zhang; Baoying Hu; Fei Qian

doi:10.3389/fonc.2022.850767

High Expression of CSF-1R Predicts Poor Prognosis and CSF-1R^high Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma

Front Oncol. 2022 Apr 4:12:850767. doi: 10.3389/fonc.2022.850767. eCollection 2022.

Authors

Xingchao Wang¹, Jianfeng Zhang², Baoying Hu³, Fei Qian¹

Affiliations

¹ Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China.
² Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.
³ Department of Immunology, Medical College, Nantong University, Nantong, China.

Abstract

Background: Colony stimulating factor 1 receptor (CSF-1R) is a single channel III transmembrane receptor tyrosine kinase (RTK) and plays an important role in immune regulation and the development of various cancer types. The expression of CSF-1R in colon adenocarcinoma (COAD) and its prognostic value remain incompletely understood. Therefore, we aim to explore the prognostic value of CSF-1R in COAD and its relationship with tumor immunity.

Methods: CSF-1R expression in a COAD cohort containing 103 patients was examined using immunohistochemistry (IHC). The relationship between CSF-1R expression and clinicopathological parameters and prognosis was evaluated. Dual immunofluorescence staining was conducted to determine the localization of CSF-1R in COAD tissues. Univariate and multivariate Cox regression analysis were performed to evaluate independent prognostic factors. Transcriptomic profiles of CSF-1R^high and CSF-1R^low tumor-associated macrophages (TAMs) were investigated. Gene enrichment analysis was used to explore the signal pathways related to CSF-1R. In addition, the relationship between CSF-1R in tumor microenvironment (TME) and tumor immunity was also studied.

Results: IHC analysis showed that CSF-1R was overexpressed in COAD, and higher expression was associated with shorter overall survival (OS). Immunofluorescence staining showed that CSF-1R was co-localized with macrophage marker CD68. Univariate and multivariate Cox regression analysis showed that CSF-1R was an independent prognostic factor for COAD. The results of gene enrichment analysis showed that CSF-1R was involved in tumor immune response and regulation of TME. In addition, CSF-1R was significantly correlated with TME, immune cell infiltration, TMB, MSI, Neoantigen, and immune checkpoint molecules.

Conclusion: CSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.

Keywords: CSF-1R; colon adenocarcinoma; pathway; prognosis; tumor immunity.