BackgroundProgrammed cell death 1 (PD-1) is a key cell-surface receptor of CD28 superfamily that triggers inhibitory pathways to attenuate T-cell responses and promote T-cell tolerance. As a crucial role in tumor immunity, PD-1 has been a focus of studies in anti-cancer therapy. It has been approved that tumors could exploit PD-1-dependent immune suppression for immune evasion. Considering the wide use of glucocorticoids (GCs) in anti-cancer therapy and their immunosuppressive effects, we explored whether GCs could influence the expression of PD-1.ResultsIn our study, we used dexamethasone (DEX) as a model glucocorticoid and demonstrated that DEX could enhance PD-1 expression in a dose-dependent manner. The effects were completely inhibited by the glucocorticoid receptor (GR) antagonist mifepristone (RU486), indicating that the effect of DEX on PD-1 is mediated through GR. We further found the sensitivity to DEX-induced upregulation of PD-1 expression had a significant difference between different T cell subsets, with memory T cells more susceptible to this effect. We also showed that DEX could suppress T cell functions via inhibition of cytokines production such as IL-2, IFN-γ, TNF-α and induction of apoptosis of T cells.ConclusionOur findings suggest a novel way by which DEX suppress the function of activated T lymphocytes by enhancing expression of PD-1 and provide an insight into the optimum clinical application of GCs.

AMD1 could stabilize the interaction of IQGAP1 with FTO. The interaction with IQGAP1 increases FTO phosphorylation and expression. High level of FTO promotes pluripotency factors expression and elevates stem cell-like property of HCC cells.

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The discovery of epidermal growth factor receptor (EGFR)‑sensitive mutations in non‑small cell lung cancer (NSCLC) and the successful clinical application of EGFR tyrosine kinase inhibitors (TKIs) have changed the regimen of lung cancer therapy from traditional cytotoxic chemotherapy to molecular‑targeted cancer therapy. However, the main limitation of EGFR‑TKI therapy is the heterogeneity of lung cancer harboring EGFR‑sensitive mutations. In addition, the synergistic effect of the administration of chemotherapy and EGFR‑TKIs, combined with tumor heterogeneity, on NSCLC remains unclear. The present study aimed to investigate the optimal schedule for combined treatment with paclitaxel/gemcitabine and gefitinib in co‑cultured NSCLC cell lines, in which PC9 cells were mixed with A549 cells at 0:1, 1:19, 1:3, 1:1, 3:1 and 1:0 ratios, and clarified the associated mechanisms. The mixed cells were used to simulate the tumor heterogeneity in the human cancer environment and to define the differential anti‑proliferative effects of nine schedules of paclitaxel/gemcitabine and gefitinib, based on cell cycle distribution. We confirmed that gefitinib arrested PC9 cell growth, mainly at the G1 phase, at 24 h regardless of low or high concentration. After a 24‑h culture in gefitinib‑free medium, the cell cycle returned to its normal state. Paclitaxel and gemcitabine induced G2/M phase and S phase arrest at 72 h, respectively. The anti‑proliferative effect of paclitaxel/gemcitabine followed by gefitinib resulted in the optimum anti‑proliferative activity compared with the other seven schedules, which was not affected by tumor heterogeneity. Cell cycle‑dependent synergism may contribute to this effect. Our results are in accordance with most of the existing clinical trials, and could provide a potential treatment option for patients with advanced NSCLC and for the ongoing clinical investigation of the sequential treatment of NSCLC.

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Mutations of epidermal growth factor receptor (EGFR) gene are good predictors of response to treatment with EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC). It is well established that classic mutations, such as in-frame deletions in exon 19 and the point mutation L858R in exon 21, are associated with high sensitivity to EGFR TKIs. Though mutations in exon 20 are almost correlated with EGFR-TKIs resistance, the awareness that they might confer sensitivity to TKI treatment should be emphasized. Herein, we describe a novel mutation in exon 20 of EGFR in a Chinese male non-smoker, who was diagnosed with stage IV lung adenocarcinoma and characterized by the codon 769 point mutation GTG>GCG, which translates into alanine instead of valine (p.V769A). In this case, the patient showed a good clinical response to erlotinib after paclitaxel/cisplatin first-line and docetaxel second-line chemotherapies. Therefore, we suggest that this rare mutation (p.V769A) may be a sensitive EGFR mutation in NSCLC. The identification of novel EGFR mutations provides new predictive biomarkers for TKI treatment and is essential to the successful use of targeted therapies.

Our study demonstrated that tumor cells expressing H protein could activate the immune memory response against MV, which exerted specific anti-tumor effects, and indicated that the MV-H gene can be used as a potential therapeutic gene for cancer gene therapy.