M2-like polarized tumor-associated macrophages (TAMs) are the major component of infiltrating immune cells in hepatocellular carcinoma (HCC), which have been proved to exhibit significant immunosuppressive and pro-tumoral effects. However, the underlying mechanism of the tumor microenvironment (TME) educating TAMs to express M2-like phenotypes is still not fully understood. Here, we report that HCC-derived exosomes are involved in intercellular communications and exhibit a greater capacity to mediate TAMs’ phenotypic differentiation. In our study, HCC cell-derived exosomes were collected and used to treat THP-1 cells in vitro. Quantitative polymerase chain reaction (qPCR) results showed that the exosomes significantly promoted THP-1 macrophages to differentiate into M2-like macrophages, which have a high production of transforming growth factor-β (TGF-β) and interleukin (IL)-10. The analysis of bioinformatics indicated that exosomal miR-21-5p is closely related to TAM differentiation and is associated with unfavorable prognosis in HCC. Overexpressing miR-21-5p in human monocyte-derived leukemia (THP-1) cells induced down-regulation of IL-1β levels; however, it enhanced production of IL-10 and promoted the malignant growth of HCC cells in vitro. A reporter assay confirmed that miR-21-5p directly targeted Ras homolog family member B (RhoB) 3′-untranslatedregion (UTR) in THP-1 cells. Downregulated RhoB levels in THP-1 cells would weaken mitogen-activated protein kinase (MAPK) axis signaling pathways. Taken together, tumor-derived miR-21-5p promote the malignant advance of HCC, which mediated intercellular crosstalk between tumor cells and macrophages. Targeting M2-like TAMs and intercepting their associated signaling pathways would provide potentially specific and novel therapeutic approaches for HCC treatment.

No abstract

BackgroundThe aim of this study is to assess the clinical benefit of postoperative radiotherapy (PORT) in patients with esophageal cancer (EC) who treated with neoadjuvant chemotherapy (NAC) and surgery via a national population-based database.MethodsPatients diagnosed with EC between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was used to compare the overall survival (OS) and cause-specific survival (CSS) difference between PORT vs. no-radiotherapy (RT) groups before and after propensity score matching (PSM). After PSM for baseline characteristics, Cox proportional hazard regression was performed to investigate the factors associated with OS.ResultsA total of 321 patients were included in the analysis. Of them, 91 patients (28%) received PORT. In the unmatched population, the no-RT group had improved OS compared with PORT (44 vs. 25 months, p = 0.002), and CSS was similar in patients undergoing NAC with or without PORT (42 vs. 71 months, p = 0.17). After PSM for baseline characteristics, the OS benefit of the no-RT group over the PORT group remained significant with a median OS of 46 vs. 27 months (p = 0.02), and CSS remained comparable between groups (83 vs. 81 months, p = 0.49). In subgroup analyses, PORT did not improve the OS among patients with adenocarcinoma in the subgroups of cN0, cN1, and cN2–3 (all p > 0.05). In Cox regression, aged ≥71 years old, cT3–4, cN2–3, and receiving PORT were independent predictors of worse OS, whereas cT4 and cN2–3 were independent predictors of worse CSS (all p < 0.05).ConclusionsThe present study demonstrated that no survival benefit could be obtained from the additional use of PORT after NAC and surgery in patients with EC. Well-designed prospective trials are needed to confirm our findings.