Changes of systemic immune response after stereotactic ablative radiotherapy (SABR) - first results of a prospective study in early lung cancer patients

Abstract

INTRODUCTION Non‑small cell lung cancer (NSCLC) is the most common lung tumor. Conventional conservative treatment in medically inoperable patients with early stage NSCLC has poor outcome. To improve treatment efficacy, stereotactic ablative radiotherapy (SABR) has been developed, which enables the delivery of high‑dose radiation to the tumor. OBJECTIVES This prospective study was conducted to test the hypothesis that a sudden death of cancer cells after SABR may lead to changes in systemic immune response. PATIENTS AND METHODS We enrolled 89 treatment‑naive patients with stage T1/2aN0 NSCLC. All patients received SABR, in accordance with treatment standards at our department. Blood samples were collected 3 times: before treatment (n = 89), and then at 2 (n = 86) and 12 weeks (n = 75) after treatment completion to assess the proportion of CD4(+) and CD8(+) T cells, and the expression of T‑lymphocyte transcription factors: T‑bet, GATA‑3, ROR‑γt, and FoxP3. Serum C‑reactive protein (CRP) levels, absolute neutrophil count (ANC), absolute lymphocyte count, and white blood cell (WBC) count were measured to exclude the impact of nonspecific inflammatory reaction. The expression levels of lymphocyte antigens were measured by flow cytometry. RESULTS Serum CRP levels, ANC, and WBC count remained stable during the study. We observed slight lymphopenia, which correlated with irradiated lung volume. After SABR, the proportion of CD8(+), CD4(+), as well as the proportion of CD4(+) T cells expressing GATA‑3(+), T‑bet(+), or ROR‑γt(+) increased, while the number of CD4(+)FoxP3(+) cells (specific for regulatory T cells) decreased. CONCLUSIONS Our findings may suggest that SABR enhances the systemic immune response by increasing the proportion of proinflammatory T‑cell subpopulations.