Dynamic alterations of myeloid-derived suppressor cells and CD68+CD163+M2-like macrophages of non-small cell lung cancer patients in radiotherapy

BackgroundRecent studies showed that myeloid-derived suppressor cells (MDSCs) and M2-like macrophages are involved in the treatment of non-small cell lung cancer (NSCLC) as immunosuppressive cells; however, the changes of MDSCs and M2-like macrophages, and their prognostic value are rarely unknown in NSCLC patients during radiotherapy. In this article, we aim to explore dynamic alteration of the circulating MDSCs and M2-like macrophages, to examine their relationship, and to evaluate their prognostic value for NSCLC patients in radiotherapy.Method:Peripheral blood mononuclear cells from healthy controls and NSCLC patients in radiotherapy were isolated to examine the circulating MDSCs and M2-like macrophages. The peripheral MDSCs defined as CD11b+CD33+HLA-DR− and M2-like Macrophages signified as CD68+CD163+ were determined by flow cytometry. 40 plasma inflammatory cytokines were measured by multiplex ELISA.ResultsCompared with health controls, the percentages of MDSCs and CD68+CD163+M2-like macrophages of NSCLC patients were significantly elevated, and were distinctly higher in NSCLC patients in radiotherapy than in pre-radiotherapy. Moreover, MDSCs correlated positively with CD68+CD163+M2-like macrophages in NSCLC patients in radiotherapy and post-radiotherapy. Interestingly, the alterations of the percentages of MDSCs and CD68+CD163+M2-like macrophages in RT were irrelated with radiotherapy area. During radiotherapy, the proportions of MDSCs were clearly increased in adenocarcinoma patients but not in squamous carcinoma patients, while the proportions of CD68+CD163+M2-like macrophages were markedly elevated in squamous carcinoma patients but not in adenocarcinoma patients. In addition, the percentages of MDSCs and CD68+CD163+ M2-like macrophages were also increased in NSCLC patients reached PR in radiotherapy compared to NSCLC patients reached SD and PD. IL-1ra and MIP-1β have a positive relation with MDSCs or M2 macrophages in NSCLC patients in radiotherapy, and Eotaxin was correlated with CD68+CD163+M2-like macrophages but not MDSCs in NSCLC patients after radiotherapy.ConclusionsThe dynamic alterations of MDSCs and M2-like macrophages, as well as their connection with plasm inflammation cytokines, could provide potentially prognostic and sensitive markers for NSCLC patients in radiotherapy.Trial Registration: Jinshan Hospital of Fudan University, IEC-2020-S01. Registered 22 May 2020.