Effect of chemoradiotherapy on the proportion of circulating lymphocyte subsets in patients with limited-stage small cell lung cancer

Abstract

Objective: Chemoradiotherapy (CRT) is the standard treatment for limited-stage small cell lung cancer (LS-SCLC), which can exert anti-tumor effects by regulating immune cells. Different immune cell subsets are associated with a specific sensitivity to CRT. The purpose of this study was to characterize the proportion or composition of peripheral lymphocytes in patients with LS-SCLC before and after CRT, and evaluate their prognostic value.

Methods: A total of 98 patients with LS-SCLC were enrolled. The expression of CD3, CD4, CD8, CD45RA, CD45RO, CD38, CD56, and CD19 on the surface of peripheral blood cells was detected by flow cytometry and retrospectively analyzed. The relationship between the proportion of lymphocyte subsets, progression-free survival (PFS), and overall survival (OS) was evaluated using a log-rank test and Cox regression model.

Results: The median PFS was 12.3 months and the median OS was 21.7 months. Compared with the pre-treatment specimens, post-treatment lymphocytes had increased proportions of CD3⁺, CD3⁺CD8⁺, CD8⁺CD38⁺ T cells, and NKT cells, and a decreased proportion of CD3⁺CD4⁺ T cells, CD4⁺CD45RA⁺ T cells, B cells, NK cells, and CD4/CD8 ratio. Univariate and multivariate analyses showed that prophylactic cranial irradiation, high percentages of CD4⁺CD45RA⁺, CD8⁺CD38⁺ T cells after CRT independently predicted superior PFS. Male patients with a high baseline CD4⁺CD45RO⁺ T cell ratio predicted a poor OS.

Conclusions: CRT induced changes in the proportion of circulating lymphocyte subsets in LS-SCLC, which is helpful for designing a regimen of immune drugs to be combined with CRT. The prognostic value of the proportion of lymphocytes aids in understanding the role of peripheral immune profiles in LS-SCLC.

Keywords: Chemoradiotherapy; Lymphocyte subsets; Small cell lung cancer.

Fig. 1

Percentages of lymphocyte subsets in peripheral blood before and after chemoradiotherapy in LS-SCLC patients. A two related sample nonparametric test was used for statistical analysis and the charts represented the median % (min to max) deviation for the proportion of each lymphocyte during treatment. The baseline values represented those prior to any treatment. Post-CRT represented the values at three months after chemoradiotherapy. The dotted line represents the normal reference range

Fig. 2

The proportion of circulating high CD8⁺ T cells in 45 patients. After chemoradiotherapy, a the proportion of peripheral CD8⁺ T cells in 45 patients was higher than the normal value (12.0–38.0%), and b the CD4/CD8 ratio was lower than reference range (1.3–3.5%). Among them, the percentages of CD4⁺ T cells were c normal in 20 cases and e low in 25 cases (normal range, 29.0–60.0%), d, f the proportion of CD3⁺ T cells in all patients was normal or higher than 84.0% (60.0–84.0%). The red dotted line represents the normal high value and the blue dotted line represents the normal low value

Fig. 3

The relationship between the changes of a CD8⁺CD38⁺ T cells and b CD19⁺ B cells and the factors of chemoradiotherapy

Fig. 4

Progression-free survival (PFS) and overall survival (OS) of patients with LS-SCLC. Stratifications were based on the median proportation of lymphocytes and patient clinical characteristics. a Kaplan–Meier curve of PFS for patients with or without PCI treatment. b Kaplan–Meier curve of PFS for patients with the CD4⁺CD45RA⁺ T cell ratio after CRT. c Kaplan–Meier curve of PFS for patients with the CD8⁺CD38⁺ T cell ratio after CRT. d Kaplan–Meier curve of OS for male and female patients. e Kaplan–Meier curve of OS for patients with the baseline CD4⁺CD45RO⁺ T cell ratio