Changes in PD-1 expression on T lymphocyte subsets and related immune indicators before and after definitive chemoradiotherapy for esophageal squamous cell carcinoma

Abstract

Objective: This study aimed to observe the dynamic changes in the expression of T lymphocytes, natural killer (NK) cells, and PD-1 in patients with first-diagnosed esophageal squamous cell carcinoma (ESCC) before and after chemoradiotherapy (CRT) and evaluate the impact of PD-1 expression in peripheral blood on the short-term outcome of patients with ESCC.

Patients and methods: Seventy-three patients with ESCC who were treated with definitive CRT were enrolled. Before and after CRT, flow cytometry was used to detect thePD-1 expression in the peripheral blood and related immune indicators. Peripheral blood from 10 healthy individuals was used as control.

Results: The percentages of CD3⁺ (p = 0.018), CD4⁺ (p < 0.001), and CD8⁺ T cells (p < 0.001); NK cells (p = 0.009); and the CD4⁺/CD8⁺ ratio (p < 0.001), as well as PD-1⁺CD3⁺ (p < 0.001), PD-1⁺CD4⁺ (p < 0.001), and PD-1⁺CD8⁺ (p < 0.001) T cells, before CRT significantly differed from those in the post-CRT group. The percentages of PD-1⁺CD8⁺ T cells differed significantly between the radiotherapy alone and CRT groups (p < 0.05). PD-1 expression in CD3⁺, CD4⁺, and CD8⁺ T cells significantly decreased in patients achieving overall response rate (all p < 0.05). Compared with those in the incomplete response group, PD-1⁺CD8⁺ T cells significantly decreased in the CR group (p < 0.05).

Conclusion: CRT aggravated immunosuppression and increased PD-1 expression in T lymphocyte subsets in patients with ESCC, possibly related to the radiation field. PD-1 expression in T lymphocyte subsets can predict short-term outcomes in patients and provide a theoretical basis for the sequential application of PD-1 immunosuppressants after radiotherapy and chemotherapy.

Keywords: NK cells; PD-1; T lymphocyte subsets; chemoradiotherapy; esophageal squamous cell carcinoma; immunotherapy.

Figure 1.

Flow chart of T lymphocyte subsets, PD-1, and NK cells. (a) The box on the right side represents the proportion of CD3⁺ cells, that is, T lymphocytes. (b) The box in Q1 represents the proportion of CD3⁺CD8⁺ cells, that is, CD8⁺ T cells, whereas the box in Q3 represents the proportion of CD3⁺CD4⁺ cells, that is, CD4⁺ T cells. (c) The circle in the box represents the proportion of CD3^-CD16⁺CD56⁺ cells, that is, NK cells. (d) The circle in the box represents the proportion of CD3⁺CD279⁺ cells. The proportion represents that of PD-1 expression among the total T cells. (e) The proportion of CD4⁺CD279⁺ cells circled in the box represents that of PD-1 expression in CD4⁺ T cells. (f) The circle in the box represents the proportion of CD8⁺CD279⁺ cells, representing the proportion of PD-1 expression among CD8⁺ T cells.

Figure 2.

Comparison of NK cells and T lymphocyte subsets between patients with esophageal squamous cell carcinoma and healthy controls for. T test level, *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 3.

Comparison of PD-1 expression on T lymphocyte subsets between patients with esophageal squamous cell carcinoma and healthy controls. T test level, *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 4.

Correlation of PD-1 expression in T lymphocyte subsets. (a) PD-1 expression on CD3⁺ T cells vs. PD-1 expression on CD4⁺ T cells. (b) PD-1 expression on CD3⁺ T cells vs. PD-1 expression on CD8⁺ T cells. (c) PD-1 expression on CD4⁺ T cells vs. PD-1 expression on CD8⁺ T cells. r = Pearson correlation coefficient; p < 0.05, correlation analysis shows statistical significance.