Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo. Results UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model. Conclusions UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment. Electronic supplementary material The online version of this article (10.1186/s12943-019-1032-0) contains supplementary material, which is available to authorized users.

Natural killer (NK) cells are important in host to eliminate circulating tumour cells (CTCs) in turn preventing the development of tumour cells into metastasis but the mechanisms are very poorly defined. Here we find that the expression level of miR-296-3p is much lower in the non-metastatic human prostate cancer (PCa) cell line P69 than that in the highly metastatic cell line M12, which is derived from P69. We demonstrate that miR-296-3p directly targets and inhibits the expression of intercellular adhesion molecule 1 (ICAM-1) in the malignant M12. The data from clinical tissue microarrays also show that miR-296-3p is frequently upregulated and ICAM-1 is reversely downregulated in PCa. Interestingly, ectopic expression of miR-296-3p in P69 increases the tolerance to NK cells whereas knockdown of miR-296-3p in M12 reduces the resistance to NK cells, which both phenotypes can be rescued by re-expression or silencing of ICAM-1 in P69 and M12, respectively. These results are also manifested in vivo by the decrease in the incidence of pulmonary tumour metastasis exhibited by knockdown of miR-296-3p in M12 when injected into athymic nude mice via tail vein, and consistently down-expression of ICAM-1 reverses this to increase extravasation of CTCs into lungs. Above results suggest that this newly identified miR-296-3p-ICAM-1 axis has a pivotal role in mediating PCa metastasis by possible enhancing survival of NK cell-resistant CTC. Our findings provide novel potential targets for PCa therapy and prognosis.

Advanced gastric cancer (AGC) has high morbidity and mortality in East Asia, and it is urgent to explore new treatments to improve patient prognosis. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have exhibited remarkable activity in clinical trials and were approved by the FDA for clinical therapy in several types of tumors. Here, we evaluated PD-L1 expression and T cell infiltration in AGC. Positive tumor PD-L1 expression was detected in 171 AGCs (33.60%) out of 509 AGCs. PD-L1 expression was positively correlated with CD8+ T cell infiltration. Then, PD-L1 and CD8A mRNA expression was analyzed using gastric cancer data from the TCGA database, confirming a positive correlation. Patient survival was assessed according to PD-L1 status and the T cell infiltration density. PD-L1 expression and a high density of CD8+ T cells in AGCs were associated with improved prognosis, whereas no significant difference was noted between PD-1 and CD3 expression. In contrast, a high density of FOXP3+ T cells in AGCs indicated a poor prognosis. Multivariate Cox regression analysis revealed that CD8+ T cell density acts as an independent predictor of overall survival (OS) in AGC patients. Taken together, this study further highlights targets for immune checkpoint-based therapy in AGC.

Background: Liver is one of the most preferred destinations of distant metastasis in gastric cancer (GC). As effective treatment is still limited, the prognosis of GC patients bearing liver metastasis is poor. We filter out lysyl oxidase (LOX) to study its function in the tumor microenvironment (TME) and seek for potential therapeutic targets. Methods: Transcription analysis on 6 cases of liver metastasis of GC patients with respective paired primary tumors and adjacent normal livers was performed. The filtration out of LOX was done using 5 datasets. 69 GC liver metastasis tissues were utilized to perform immunohistochemistry (IHC) and analyze prognosis. Computed Tomography (CT) combined 3D organ reconstruction bioluminescence imaging was performed to precisely evaluate the metastatic tumor burden on liver of intrasplenic injection mouse model. Human and mouse cancer associated fibroblasts (CAFs) in liver metastasis were separated to culture to study the interaction of LOX and TGF-β1. Patients-derived xenograft (PDX) model was established using liver metastasis of patients to evaluate the therapeutic value of LOX inhibitor β-aminopropionitrile (BAPN). Results: CAFs-derived LOX at liver metastatic niche of GC promotes niche formation and outgrowth thus predicts poor prognosis. Meanwhile tumor cells in niche secrete TGF-β1 to nourish CAFs and stimulate them to produce more LOX in turn. The mechanism involved in LOX-mediated proliferation facilitation is enhancement of Warburg effect. The inhibitor of LOX, BPAN could hamper the effect brought by LOX in vivo and in vitro. Interpretation: Our study has unveiled a positive feedback loop between CAFs and tumor cells in liver metastasis niche of GC. The core molecule is LOX which facilitates Warburg effect. Targeting LOX with its inhibitor BAPN might serve as a potential therapeutic strategy.