Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells which are abnormally accumulated during the differentiation of myeloid cells. Immunosuppression is the main functional feature of MDSCs, which inhibit T cell activity in the tumor microenvironment (TME) and promote tumoral immune escape. The main principle for immunotherapy is to modulate, restore, and remodel the plasticity and potential of immune system to have an effective anti-tumor response. In the TME, MDSCs are major obstacles to cancer immunotherapy through reducing the anti-tumor efficacy and making tumor cells more resistant to immunotherapy. Therefore, targeting MDSCs treatment becomes the priority of relevant studies and provides new immunotherapeutic strategy for cancer treatment. In this review, we mainly discuss the functions and mechanisms of MDSCs as well as their functional changes in the TME. Further, we review therapeutic effects of immunotherapy against MDSCs and potential breakthroughs regarding immunotherapy targeting MDSCs and immune checkpoint blockade (ICB) immunotherapy.

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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature cells derived from bone marrow that play critical immunosuppressive functions in the tumor microenvironment (TME), promoting cancer progression. According to base length, Non-coding RNAs (ncRNAs) are mainly divided into: microRNAs (miRNAs), lncRNAs, snRNAs and CircRNAs. Both miRNA and lncRNA are transcribed by RNA polymerase II, and they play an important role in gene expression under both physiological and pathological conditions. The increasing data have shown that MiRNAs/LncRNAs regulate MDSCs within TME, becoming one of potential breakthrough points at the investigation and treatment of cancer. Therefore, we summarize how miRNAs/lncRNAs mediate the differentiation, expansion and immunosuppressive function of tumor MDSCs in TME. We will then focus on the regulatory mechanisms of exosomal MicroRNAs/LncRNAs on tumor MDSCs. Finally, we will discuss how the interaction of miRNAs/lncRNAs modulates tumor MDSCs.

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.

PurposeThe purpose of this study is to explore whether the down-regulation of ALOX15 is related to the stage, differentiation and prognosis of lung adenocarcinoma, whether the overexpression of ALOX15 can inhibit tumor proliferation and metastasis, and whether it is related to the functional target of lung adenocarcinoma(LUAD).MethodsFirstly, bioinformatics of lung cancer patients was analyzed using the TCGA database to study the differential expression of ALOX15 in LUAD and its effect on the survival of LUAD. Then, 50 clinical tissue samples of LUAD were collected to detect the expression of ALOX15 and its relationship with the differentiation degree and stage of lung cancer. Finally, the relationship between the expression of ALOX15 and the proliferation and differentiation of LUAD cell lines (NCI-H1944, A549, PC9) with different degrees of differentiation and the construction of ALOX15 overexpression stable lines was detected.ResultsALOX15 bioinformatics analysis showed that ALOX15 decreased significantly in the early stage of LUAD and had no correlation with the survival of lung cancer patients. ALOX15 was downregulated in LUAD with low differentiation and metastasis in LUAD. LUAD cell lines showed that the lower the degree of differentiation, the lower the expression of ALOX15, and the overexpression of ALOX15 in LUAD cells inhibited the proliferation and migration of cancer cells.ConclusionThese results suggest that the expression of ALOX15 is closely related to the differentiation, proliferation, and metastasis of LUAD, and that upregulation of ALOX15 may inhibit the development of LUAD, suggesting that ALOX15 is a potential biological therapeutic target.Author summaryWhy was this study done?Lung cancer is one of the most frequently diagnosed cancers in the world and the leading cause of cancer-related deaths worldwide.Lung cancer is a heterogeneous disease with a wide range of clinicopathologic features. Lung cancer is roughly divided into non-small cell lung cancer (85% of all diagnoses) and small cell lung cancer (15% of all diagnoses). Adenocarcinoma is a common subtype of non-small cell lung cancer, and its recurrence rate is high, and the prognosis is poor. Therefore, the pathogenesis and characteristics of adenocarcinoma are studied and explored.What did the researchers do and find?Biological information database was used to analyze the expression level of arachidonic acid-15-lipoxygenase (ALOX15) in lung adenocarcinoma, and then the expression differences were discussed through clinical samples and cell experiments.Low ALOX15 expression was detected in lung adenocarcinoma (LAUD) patients compared with normal tissues, and ALOX15 levels influenced LUAD development.By infecting A549 with lentivirus and overexpressing ALOX15 of A549 and PC-9 with PC9, it was found that ALOX15 inhibited the proliferation of tumor cellsWhat do these findings mean?arachidonic acid-15-lipoxygenase may be one novel potential biomarker for LUAD and a potential therapeutic target