Detection and quantification of microplastics in various types of human tumor tissues.

Microplastics (MPs) have been detected in various human tissues. However, whether MPs can accumulate within tumors and how they affect the tumor immune microenvironment (TIME) and therapeutic responses remains unclear. This study aimed to determine the presence of MPs in tumors and their potential effects on the TIME. Sixty-one tumor samples were collected for analysis. The presence of MPs in tumors was qualitatively and quantitatively assessed using pyrolysis-gas chromatography-mass spectrometry. MPs were detected in 26 of the samples examined. Three types of MPs were identified: polystyrene, polyvinyl chloride, and polyethylene. In lung, gastric, colorectal, and cervical tumors, the MP detection rates were 80 %, 40 %, 50 %, and 17 % (7.1-545.9 ng/g), respectively. MPs were detected in 70 % of pancreatic tumors (18.4-427.1 ng/g) but not detected in esophageal tumors. In pancreatic cancer, the MP-infiltrated TIME exhibited a reduction in CD8+ T, natural killer, and dendritic cell counts, accompanied by substantial neutrophil infiltration. This study illustrates the potential presence of MPs in diverse tumors; varying adhesive affinities were observed among different tumor types. MPs may lead to a more adverse TIME in pancreatic tumors. Further investigations are warranted to assess whether MPs promote tumor progression and affect the efficacy of immunotherapy.

Polystyrene microplastics aggravate radiation-induced intestinal injury in mice.

Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 µg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients' daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.

Single-cell Transcriptomic Analysis Reveals an Immunosuppressive Network Between POSTN CAFs and ACKR1 ECs in TKI-resistant Lung Cancer.

BACKGROUND/AIM: Tyrosine kinase inhibitor (TKI) therapy, a principal treatment for advanced non-small cell lung cancer (NSCLC), frequently encounters the development of drug resistance. The tumor microenvironment (TME) plays a critical role in the progression of NSCLC, yet the relationship between endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) subpopulations in TKI treatment resistance remains largely unexplored. MATERIALS AND METHODS: The BioProject database PRJNA591860 project was used to analyze scRNA-seq data including 49 advanced-stage NSCLC samples across three different time points: pre-targeted therapy (naïve), post-partial response (PR) to targeted therapy, and post-progressive disease (PD) stage. The data involved clustering stromal cells into multiple CAFs and ECs subpopulations. The abundance changes and functions of each cluster during TKI treatment were investigated by KEGG and GO analysis. Additionally, we identified specific transcription factors and metabolic pathways via DoRothEA and scMetabolism. Moreover, cell-cell communications between PD and PR stages were compared by CellChat. RESULTS: ECs and CAFs were clustered and annotated using 49 scRNA-seq samples. We identified seven ECs subpopulations, with OIT3 ECs showing enrichment in the PR phase with a drug-resistance phenotype, and ACKR1 ECs being prevalent in the PD phase with enhanced cell adhesion. Similarly, CAFs were clustered into 7 subpopulations. PLA2G2A CAFs were predominant in PR, whereas POSTN CAFs were prevalent in PD, characterized by an immunomodulatory phenotype and increased collagen secretion. CellChat analysis showed that ACKR1 ECs strongly interacted with macrophage through the CD39 pathway and POSTN CAFs secreted Tenascin-C (TNC) to promote the progression of epithelial cells, primarily malignant ones, in PD. CONCLUSION: This study reveals that POSTN CAFs and ACKR1 ECs are associated with resistance to TKI treatment, based on single-cell sequencing.