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

**Authors:** Dehua Kong, Chunyan Gao, Yang Yu, Lu Yang, Ji Ma, Shimin Tang, Ying Mao, Yong Li, Na Li

PMC · DOI: 10.1371/journal.pone.0325349 · 2025-06-30

## TL;DR

This study explores how immune cells related to the PD-1 pathway are distributed in esophageal cancer tissues and how their presence affects patient survival.

## Contribution

The study introduces a new prognostic model for esophageal cancer based on PD-1 pathway immune cell markers and lymph node metastasis.

## Key findings

- High expression of PD-1, PD-L1, FOXP3, and CD25 correlates with deeper tumor invasion and lymph node metastasis.
- Low expression of PD-1, PD-L1, FOXP3, CD25, and high CD4/CD8 levels are linked to better three-year survival rates.
- A predictive model using these markers shows strong accuracy in assessing patient prognosis.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Genes:** PDCD1 (programmed cell death 1) [NCBI Gene 5133], CD274 (CD274 molecule) [NCBI Gene 29126], FOXP3 (forkhead box P3) [NCBI Gene 50943], IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559], CD4 (CD4 molecule) [NCBI Gene 920], CD8A (CD8 subunit alpha) [NCBI Gene 925]
- **Diseases:** esophageal cancer (MONDO:0007576)

## Full-text entities

- **Genes:** PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}
- **Diseases:** tumor (MESH:D009369), lymph node metastasis (MESH:D008207), EC (MESH:D004938)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12208471/full.md

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Source: https://tomesphere.com/paper/PMC12208471