Aberrant Alteration of Circulating Lymphocyte Subsets in Small Cell Lung Cancer Patients Treated with Radiotherapy

Abstract

Purpose: The role of different circulating lymphocyte subsets, as well as their correlation with clinical characteristics of small cell lung cancer patients have not yet been fully understood. This study aims to evaluate the influence of the fluctuating absolute numbers of lymphocyte subpopulations in peripheral blood of patients with small cell lung cancer. Methods: The absolute counts and percentages of lymphocyte subsets in peripheral blood of 329 patients with small cell lung cancer were retrospectively analyzed. The numbers of CD3⁺, CD3⁺CD4⁺, and CD3⁺CD8⁺ T lymphocytes, CD3^-CD19⁺ B lymphocytes, and CD3^-CD16⁺CD56⁺ NK cells were evaluated by flow cytometry. Their relationship with the patients' clinical characteristics were statistically evaluated. Results: The CD4/CD8 values derived from the absolute number and percentage of CD3⁺CD4⁺ cells divided by CD3⁺CD8⁺ cells were identical (1.86 ± 0.99). There was no association between any of the lymphocyte subsets levels and age/sex of the 329 patients with small cell lung cancer. The patients with advanced stage had a reduction in CD3⁺ and CD3⁺CD4⁺ T cell counts and a decreased CD4/CD8 ratio. The levels of CD3⁺CD4⁺ T cells, CD3^-CD19⁺ B cells, CD3^-CD16⁺CD56⁺ NK cells, and CD4/CD8 ratio were associated with advanced tumor-node-metastasis stage. Patients who had undergone radiotherapy were characterized by lymphopenia with lower numbers of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺ T lymphocyte, B lymphocyte, NK cell, and CD4/CD8 ratio. The evaluation of individual CD4/CD8 ratio should be combined with other clinical parameters. Conclusions: Patients with small cell lung cancer have altered lymphocyte homeostasis. Lymphopenia was a long-lasting feature of the enrolled patients who were treated with radiotherapy. The available lymphocyte subsets levels might be used to manage the clinical treatment scheme.

Keywords: immune status; lymphocyte subsets; lymphopenia; radiotherapy; small cell lung cancer.

Figure 1.

Absolute numbers of lymphocyte subpopulations and CD4/CD8 values across tumor stage and myelosuppression in SCLC patients. The bar indicates median value; the box represents the (10-90) % range. CD3⁺, T lymphocytes; CD3⁺CD4⁺, T helper/inducer cells; CD3⁺CD8⁺, cytotoxic T cells, CD3⁻CD19⁺, B lymphocytes; CD3⁻CD16⁺CD56⁺, natural killer cells.

Figure 2.

A: ROC curve for the absolute number of lymphocyte subpopulations in SCLC with or without radiotherapy. B: ROC curve for the absolute number of lymphocyte subpopulations in SCLC and control group. CD3⁺, T lymphocytes; CD3⁺CD4⁺, T helper/inducer cells; CD3⁺CD8⁺, cytotoxic T cells, CD3⁻CD19⁺, B lymphocytes; CD3⁻CD16⁺CD56⁺, natural killer cells; ROC,  receiver operating characteristic.

Figure 3.

The influence of radiotherapy on the absolute number of lymphocyte subpopulations in patients with SCLC. The patients who experienced radiotherapy (n = 130) are compared with those unexperienced cases (n = 199). The bar indicates median value; the box represents the (10-90) % range. CD3⁺, T lymphocytes; CD3⁺CD4⁺, T helper/inducer cells; CD3⁺CD8⁺, cytotoxic T cells, CD3⁻CD19⁺, B lymphocytes; CD3⁻CD16⁺CD56⁺, natural killer cells.

Figure 4.

Absolute number of lymphocyte subpopulations across the degree of myelosuppression in SCLC patients with or without radiotherapy. The bar indicates median value; the box represents the (10-90) % range. CD3⁺, T lymphocytes; CD3⁺CD4⁺, T helper/inducer cells; CD3⁺CD8⁺, cytotoxic T cells, CD3⁻CD19⁺, B lymphocytes; CD3⁻CD16⁺CD56⁺, natural killer cells.

Figure 5.

Distribution of the individual absolute CD4⁺ and CD8⁺ T cells of SCLC patients. (A) tumor stage, (B) sex, (C) tumor extent, (D) smoking history, (E) radiotherapy, (F) control group. The circle depict the prevalent appearance of the corresponding cells. The dotted line represent the normal reference range used in our laboratory. CD3+CD4+, T helper/inducer cells; CD3+CD8+, cytotoxic T cells.