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Polyvinyl Chloride Promotes Radioresistance in Hepatocellular Carcinoma by Inhibiting Radiotherapy-Induced CD8⁺ T Cell Differentiation
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Researchers found microplastics in 72% of human liver cancer (HCC) tumor samples, and specifically identified polyvinyl chloride (PVC) as an immune disruptor that blunts the cancer-killing immune response triggered by radiotherapy. PVC altered cholesterol distribution in immune cells, preventing anti-tumor CD8+ T cells from maturing properly — and a high-cholesterol diet reversed this effect, suggesting that microplastic exposure inside tumors may be actively undermining standard cancer treatments.
Radiotherapy (RT) has emerged as one of the primary treatment modalities for intermediate and advanced hepatocellular carcinoma (HCC). However, RT resistance remains widespread. Microplastics (MPs) have been detected in various tumors and may disrupt immune responses. However, evidence regarding the role of MPs in RT is scarce. Several MPs were identified in 72% (52/72) of HCC samples, among which polyvinyl chloride (PVC) impaired RT efficacy. Mechanistically, RT enhanced histone lactylation, which promoted the transcription of HMG-CoA reductase in HCC cells, thereby facilitating cholesterol synthesis and reinforcing CD8+ T cell stemness. PVC altered cholesterol localization and affected CD8⁺ T cell differentiation, which maintained a ‘cold’ tumor immune microenvironment (TIME). A high-cholesterol diet restored CD8+ T-cell stemness and improved the therapeutic response to RT in PVC-infiltrated HCC. We demonstrated that PVC could promote RT resistance. Targeting cholesterol metabolism may represent a potential combinatorial strategy to enhance the efficacy of RT in PVC-infiltrated HCC.
More Papers Like This
Polyvinyl Chloride Promotes Radioresistance in Hepatocellular Carcinoma by Inhibiting Radiotherapy-Induced CD8⁺ T Cell Differentiation
AI summary Read the abstract
This is a duplicate entry of the same study (also listed as ID 2583) finding that polyvinyl chloride microplastics were present in 72% of human liver cancer tumors and that PVC inhibits the immune response to radiotherapy by disrupting cholesterol metabolism in CD8+ T cells, potentially undermining cancer treatment outcomes.
Polyvinyl chloride promotes radioresistance in hepatocellular carcinoma by inhibiting radiotherapy-induced CD8⁺ T cell differentiation
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Scientists found microplastics in most liver cancer samples they tested, and one common type—polyvinyl chloride (PVC), found in pipes, packaging, and other everyday products—appears to make radiation therapy less effective by weakening the immune system's cancer-fighting cells. The good news: in lab studies, boosting cholesterol helped restore those immune cells and improved how well radiation worked, suggesting doctors might one day counteract this effect. This research adds to growing evidence that the tiny plastic particles we're constantly exposed to could be quietly undermining cancer treatments, making plastic pollution a health issue
Polyvinyl Chloride Promotes Radioresistance in Hepatocellular Carcinoma by Inhibiting Radiotherapy-Induced CD8⁺ T Cell Differentiation
AI summary Read the abstract
Researchers found that PVC microplastics, detected in 72% of 72 hepatocellular carcinoma tumor samples, promoted resistance to radiotherapy by inhibiting CD8+ T cell differentiation, with mechanistic analysis revealing that radiotherapy-enhanced histone lactylation upregulated HMG-CoA reductase in cancer cells to facilitate cholesterol accumulation and impair immune-mediated tumor killing.
Detection and quantification of microplastics in various types of human tumor tissues
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Researchers detected microplastics in 43% of tumor samples across lung, gastric, colorectal, cervical, and pancreatic cancers, with polystyrene, PVC, and polyethylene being the types found. In pancreatic tumors, microplastic presence was associated with fewer immune cells that fight cancer and more immune cells linked to tumor progression, suggesting microplastics may create conditions that help tumors evade the immune system.
Effects of microplastics on the colorectal tumor immune microenvironment and immunotherapy resistance via JAK–STAT–microbiota perturbation.
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Scientists found that microplastics—tiny plastic particles now common in our environment—can build up in colorectal (colon) tumors and make cancer immunotherapy less effective, based on studies in mice. The plastics seem to weaken the immune system's ability to find and attack cancer cells, partly by disrupting gut bacteria and blocking key immune signals. While this research was done in animals rather than people, it raises concerning questions about whether everyday plastic exposure could affect cancer treatment outcomes in humans.
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