The distribution characteristics of PD-1 pathway-related immune cells in esophageal cancer tissue and their prognostic significance

PLoS One. 2025 Jun 30;20(6):e0325349. doi: 10.1371/journal.pone.0325349. eCollection 2025.

Abstract

Objective: This study aims to elucidate the distribution patterns of immune cells associated with the programmed cell death protein 1 (PD-1) pathway within esophageal cancer (EC) tissues and to determine their correlation with patient prognosis.

Methods: We included tissue samples from 236 EC patients who had undergone surgery at our institution between January 2016 and January 2021. This study examined the correlation between six immunohistochemical markers and the clinical profiles of these patients. Survival analysis was performed using the Kaplan-Meier method and the LOG-rank test to evaluate the impact of immunohistochemical marker expression on patient survival. A clinical predictive model was developed and validated for prognostic assessment.

Results: Expression levels of PD-1, PD-L1, FOXP3, and CD25 were found to be positively associated with the depth of tumor invasion and lymph node metastasis (P < 0.05). In contrast, CD4 and CD8 expression levels were inversely related to these parameters (P < 0.05). High expression of PD-1, PD-L1, FOXP3, and CD25, along with lymph node metastasis, were identified as independent prognostic risk factors (P < 0.05). Patients with low expression of PD-1, PD-L1, FOXP3, CD25, and high expression of CD4 and CD8 exhibited improved three-year survival rates (P < 0.001). The predictive model, based on these factors, demonstrated high discrimination and accuracy.

Conclusion: A prognostic model incorporating the expression levels of PD-1, PD-L1, FOXP3, CD25, and lymphocyte infiltration offers robust predictive validity for the prognosis of EC patients.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / metabolism
  • Esophageal Neoplasms* / immunology
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor* / metabolism

Substances

  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • B7-H1 Antigen
  • Interleukin-2 Receptor alpha Subunit
  • Biomarkers, Tumor
  • CD274 protein, human
  • IL2RA protein, human