Metastasis is a complex process, which depends on the interaction between tumor cells and host organs. Driven by the primary tumor, the host organ will establish an environment suitable for the growth of tumor cells before their arrival, which is called the pre-metastasis niche. The formation of pre-metastasis niche requires the participation of a variety of cells, in which myeloid-derived suppressor cells play a very important role. They reach the host organ before the tumor cells, and promote the establishment of the pre-metastasis niche by influencing immunosuppression, vascular leakage, extracellular matrix remodeling, angiogenesis and so on. In this article, we introduced the formation of the pre-metastasis niche and discussed the important role of myeloid-derived suppressor cells. In addition, this paper also emphasized the targeting of myeloid-derived suppressor cells as a therapeutic strategy to inhibit the formation of pre-metastasis niche, which provided a research idea for curbing tumor metastasis.

Purpose: Immunotherapy has demonstrated durable clinical responses in various cancers by disinhibiting the immune system, largely attributed to the success of immune-checkpoint blockade. However, there are still subsets of patients across multiple cancers not showing robust responses to these agents and one significant barrier to their efficacy may be the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. In this study, we demonstrated that functional inhibition of MDSCs with (3 R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIMO), a potent PI3Kδ/γ inhibitor, enhanced the therapeutic efficacy of anti-PD1 antibody in the tumor model. Materials and methods: A syngeneic ovarian tumor model was established. MDSCs from the peripheral blood and tumor parenchyma were analyzed by flow cytometry. Proliferation and killing effects of T-lymphocytes were measured. IFNγ production was measured by ELISA assay. qPCR and western blot were used to detect the gene and protein expression. Furthermore, the therapeutic effects of TIMO combined with anti-PD1 antibody were assessed by the tumor model. Results: Our data demonstrated that inhibition of granulocytic myeloid-derived suppressor cells (G-MDSCs) function with TIMO could overcome MDSCs-mediated immunosuppression and promote antigen-specific T-lymphocyte responses, resulting in the restoration of cytotoxic T cell-mediated tumor control. We further demonstrated that TIMO and anti-PD1 combination therapy promoted tumor growth control in a syngeneic ovarian tumor model. Conclusions: Our results provided proof of concept for a new combination strategy involving the use of a selective inhibitor of PI3Kδ/γ to inhibit the function of MDSCs to enhance tumor responses to immune checkpoint blocking antibodies.

Biologically treated swine farm wastewater still contains high levels of refractory organics, humic substances and antibiotic residues, posing environmental risks and limiting opportunities for water reuse. Wastewater treatment by ozonation alone suffers from low mass transfer efficiency and selective oxidation. To overcome these limitations, a catalytic ozonation process (O₃/Fe²⁺/H₂O₂) was applied and optimized using Response Surface Methodology (RSM) based on single-factor experiments and Central Composite Design (CCD) for advanced swine farm wastewater treatment. The optimal conditions ([O₃] = 25.0 mg/L, [Fe²⁺] = 25.9 mg/L, [H₂O₂] = 41.1 mg/L) achieved a COD removal of 44.3%, which was 86.8% higher than that of ozonation alone, and increased TOC removal to 29.5%, indicating effective mineralization. Biodegradability (BOD₅/COD) of swine farm wastewater effluent increased from 0.01 to 0.34 after the catalytic ozonation treatment. Humic-like and fulvic-like substances were removed by 93.7% and 95.4%, respectively, and antibiotic degradation was significantly accelerated and enhanced. The synergistic process improved ozone utilization efficiency by 33.1% and removed 53.95% of total phosphorus through Fe³⁺-mediated coprecipitation. These findings demonstrate that with catalytic ozone decomposition and production of hydroxyl radicals, the O₃/Fe²⁺/H₂O₂ system effectively integrates enhanced ozone utilization efficiency, radical synergy, and simultaneous pollutant removal, providing a cost-effective and technically feasible strategy for advanced swine farm wastewater treatment and safe reuse.