Transcriptionally activates CCL28 expression to inhibit M2 polarization of macrophages and prevent immune escape in colorectal cancer cells

Shiquan Li; Nan Zhang; Yongping Yang; Tongjun Liu

doi:10.1016/j.tranon.2023.101842

Transcriptionally activates CCL28 expression to inhibit M2 polarization of macrophages and prevent immune escape in colorectal cancer cells

Transl Oncol. 2024 Feb:40:101842. doi: 10.1016/j.tranon.2023.101842. Epub 2023 Nov 29.

Authors

Shiquan Li¹, Nan Zhang², Yongping Yang¹, Tongjun Liu³

Affiliations

¹ Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun 130000, China.
² Department of Burn Surgery, The First Hospital of Jilin University, Changchun 130000, China.
³ Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun 130000, China. Electronic address: tongjun@jlu.edu.cn.

Abstract

Objective: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases.

Methods: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC.

Results: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression.

Conclusion: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

Keywords: CCL28; Colorectal cancer; Immune-related genes; M2 polarization of macrophages; Regulatory network; SPDEF.