The expression of PD-L1 in tumor cells is one of the main causes of tumor immune escape. However, the exact mechanism for regulating PD-L1 expression in gastric cancer (GC) cells remains unclear. Our previous studies have shown that mesenchymal stem cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells either in innate or adaptive immune system to promote tumor progress. This study aims to investigate whether GCMSCs regulate the PD-L1 expression in GC cells and explore the specific molecular mechanism. The results have shown that GCMSCs enhanced PD-L1 expression in GC cells resulting in the resistance of GC cells to CD8+ T cells cytotoxicity. However, this resistance was attenuated with IL-8 inhibition. Further studies proved that IL-8 derived from GCMSCs induced PD-L1 expression in GC cells via c-Myc regulated by STAT3 and mTOR signaling pathways. Our data indicated that blocking IL-8 derived from GCMSCs may overcome the immune escape induced by PD-L1 in GC cells and provide a potential strategy to enhance the immunotherapy efficiency in GC.

Objectives : Lung cancer in young adults is a distinct disease with particular socioeconomic implications. This study aimed to clarify the clinicopathological characteristics, best interventions, and outcomes of this distinctive entity. Methods : A retrospective review of patients with lung cancer was performed in our institute from January 2010 to June 2017. Young adults were defined as between 18 and 35 years old. Demographic, clinicopathological, therapeutic, and prognostic data were systematically analyzed. Results : From a total of 8734 patients, 120 (1.37%) were young adults, of which 82 with complete hospital records were included in this study. A high proportion had adenocarcinoma (45%) and late-stage disease (49.21% stage IV at diagnosis). Pleura (38.71%) were the most common metastatic site, followed by bone (35.48%) and lung (25.81%). The majority (68%) had single organ metastasis. Young patients had an increased frequency of gene mutations. Among the 18 patients for whom epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) status was determined, 10 had sensitive EGFR mutations while 5 had ALK rearrangement; only 3 patients were driver gene mutation-negative. The 1-year overall survival (OS) rate was 62.31% and the 3- and 5-year survival rates were both 53.31%; median OS was not achieved (range, 3-86 months). Male sex, negative or unknown gene mutation status, stage IV, and squamous or small cell lung cancer were associated with poor prognosis (OS) in early-onset lung cancer. Conclusions : Lung cancer in young adults is distinctive, with adenocarcinoma and stage IV at presentation being predominant characteristics. Gene mutation assessment should be mandatory in this subgroup due to the increased likelihood of positive driver gene alterations, as individualized targeted therapy may achieve superior outcomes.

It has been previously reported that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC)‑exosomes exhibit cardioprotective effects on the rat acute myocardial infarction (AMI) models and cardiomyocyte hypoxia injury models in vitro, however the exact mechanisms involved require further investigation. The present study aimed to investigate the repair effects of hucMSC‑exosomes on myocardial injury via the regulation of mothers against decapentaplegic homolog 7 (Smad7) expression. Compared with sham or normoxia groups (in vivo and in vitro, respectively), western blotting demonstrated that Smad7 expression was significantly decreased in the borderline area of infraction myocardium and in H9C2(2‑1) cells following hypoxia‑induced injury. Additionally, microRNA (miR)‑125b‑5p expression was markedly increased using reverse transcription‑quantitative polymerase chain reaction, but was reversed by hucMSC‑exosomes. Trypan blue staining and lactate dehydrogenase release detection demonstrated that cell injury was significantly increased in the AMI + PBS and hypoxia group compared with in the sham and normoxia groups and was inhibited by hucMSC‑exosomes. A dual luciferase reporter gene assay confirmed that Smad7 is a target gene of miR‑125b‑5p. In addition, miR‑125b‑5p mimics promoted H9C2(2‑1) cell injury following 48 h exposure to hypoxia. Downregulation of Smad7 expression under hypoxia was increased by miR‑125b‑5p mimics compared with the mimic negative control, and hucMSC‑exosomes partially alleviated this phenomenon. In conclusion, hucMSC‑exosomes may promote Smad7 expression by inhibiting miR‑125b‑5p to increase myocardial repair. The present study may provide a potential therapeutic approach to improve myocardial repair following AMI.

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Several studies show that mesenchymal stem cells (MSCs) homing to tumors not only provide the microenvironment for tumor cells but also promote tumor growth and metastasis. However, the exact mechanism remains unclear. Our study aims to investigate the role of gastric cancer MSCs (GCMSCs)-derived IL15 during GC progression. The effects of IL15 secreted by GCMSCs on GC development were evaluated by detecting the stemness, epithelial-mesenchymal transition (EMT), and migration abilities of GC cell lines. The expression of IL15 in serum and tissues of GC patients was also assessed. We found that IL15 derived from GCMSCs enhanced stemness, induced EMT and promoted migration of GC cell lines. The level of IL15 was higher in GC patients both in serum and tissues compared with that in healthy donors, which was associated with lymph node metastasis. In addition, the results have shown that IL15 in GC microenvironment was mainly produced by GCMSCs. Moreover, IL15 upregulated Tregs ratio through activation of STAT5 in CD4T cells was accompanied by elevated expression of programmed cell death protein-1 (PD-1). Our data proved that the high concentration of IL15 in tumor microenvironment, which was mainly secreted by GCMSCs, may contribute to tumor cell metastasis and offer a new opportunity to develop effective therapeutics for intercepting tumor progression.