Myeloid-Derived Suppressor Cells and CD68+CD163+M2-Like Macrophages as Therapeutic Response Biomarkers Are Associated with Plasma Inflammatory Cytokines: A Preliminary Study for Non-Small Cell Lung Cancer Patients in Radiotherapy

Abstract

Background: Recent studies show that myeloid-derived suppressor cells (MDSCs) and M2-like macrophages are involved in the treatment of tumors; however, their therapeutic response role is rarely known in non-small cell lung cancer (NSCLC) during radiotherapy. We aim to explore the dynamic alteration of the circulating MDSCs and M2-like macrophages, to examine their relationship, and to evaluate their therapeutic response value for NSCLC patients in radiotherapy.

Methods: Peripheral blood mononuclear cells from healthy controls and NSCLC patients with different radiotherapy phases were isolated to examine the circulating MDSCs and M2-like macrophages by flow cytometry. 40 plasma inflammatory cytokines were measured by multiplex ELISA.

Results: In comparison with healthy controls, the percentages of MDSCs and CD68⁺CD163⁺M2-like macrophages of NSCLC patients were significantly elevated and were distinctly higher in radiotherapy than in preradiotherapy. MDSCs were correlated positively with CD68⁺CD163⁺M2-like macrophages in NSCLC patients in radiotherapy and postradiotherapy. Especially, we found that in comparison with those in the poor group, the percentages of two cells in the good response group were markedly increased during radiotherapy and they had a significantly positive correlation. During radiotherapy, the proportions of MDSCs were clearly increased in adenocarcinoma patients and the percentages of CD68⁺CD163⁺M2-like macrophages were markedly elevated in squamous carcinoma patients. We found that after radiotherapy, the expressions of eotaxin, MIP-1β, MCP-1, and BLC were significantly increased in NSCLC patients. Further results showed that the low levels of eotaxin and TNF RII expression before radiotherapy could predict a good therapeutic response. IL-1ra and MIP-1β had a positive relation with MDSCs or CD68⁺CD163⁺M2-like macrophages in NSCLC patients during radiotherapy, and eotaxin was correlated with CD68⁺CD163⁺M2-like macrophages but not MDSCs in NSCLC patients after radiotherapy.

Conclusions: MDSCs and CD68⁺CD163⁺M2-like macrophages serve as therapeutic response biomarkers and are associated with the expressions of plasma inflammatory cytokines for NSCLC patients during radiotherapy.