Clin Colorectal Cancer. 2025 Aug 20:S1533-0028(25)00072-6. doi: 10.1016/j.clcc.2025.08.004. Online ahead of print.
ABSTRACT
BACKGROUND: The human epidermal growth factor receptor 2 (HER2) status has been proposed as a biomarker to identify colorectal cancer (CRC) patients suitable for anti-HER2 treatment. However, response varies from HER2-negative CRC, influenced by factors such as the tumors immune microenvironment (TIME) in HER2-positive CRC patients. We aimed to characterize the TIME of HER2-positive CRC by assessing the associations of inflammatory cells and prognosis.
METHODS: TIME was characterized through immunostaining for CD3, CD4, CD8, CD20, CD68, Forkhead box protein P3 (Foxp3), and programmed death-ligand 1 (PD-L1) cell densities in 36 HER2-positive and 72 HER2-negative CRC patients. HER2 positivity was evaluated by the HERACLES criteria. PD-L1 expression was evaluated by the tumor proportion score (TPS) and combined proportion score (CPS).
RESULTS: In our study, the densities of CD3, CD4, CD8, CD20, CD68, Foxp3 cells and PD-L1 expression showed no statistic differences in HER2-positive CRC patients compared to HER2-negative patients. There was a greater proportion of Foxp3+ cells (≥ 10%) among patients with HER2-positive CRC (P = .023). Although the PD-L1 CPS was correlated with sex (P = .012), inflammatory cells and the PD-L1 TPS were not correlated with clinicopathological parameters. Additionally, CRC patients with PD-L1 CPSs ≥ 1 had significantly better event-free survival (EFS) than patients with PD-L1 CPSs < 1 (P = .029). For patients with HER2-positive CRC, higher CD68 indicated better EFS (P = .047).
CONCLUSIONS: This study characterized a preliminary immune microenvironment profile and indicated CD68 increased correlation with EFS for HER2-positive CRC patients. These immune microenvironment profiles and prognostic implications could serve as potential biomarkers for stratifying patients with HER-2 positive for clinical trials.
PMID:40947372 | DOI:10.1016/j.clcc.2025.08.004
