Microplastics Trigger Antigen Presentation and CXCL1-Mediated Inflammation in Glioma Tumor-Associated Myeloid Cells 2260962

Abstract

Abstract Introduction Glioblastoma, a WHO grade IV glioma, is a lethal tumor with a 5-year survival rate below 7 percent, largely due to its immunosuppressive tumor microenvironment (TME). Tumor-associated myeloid cells contribute significantly to this immunosuppressive environment by downregulating key antigen-presenting markers, including MHC II, CD80, and CD86. Developing literature on macrophage activation indicates that microplastics, once phagocytosed, play a key role. We hypothesize that microplastic particles will activate macrophages within the tumor microenvironment after intertumoral injection. Methods To test this, we used a murine intracranial glioma model, implanted on day 0 and intratumorally injected with fluorescent microplastics 10 days after implantation. Brain and lymphoid organs were harvested 24 hours after and analyzed using flow cytometry and bulk RNA sequencing. Results Plastics directly induced upregulation of activation markers MHC II and costimulatory markers CD80 and CD86 in microplastic-treated mice compared with sham-treated mice. The largest subpopulation of myeloid cells was neutrophils, which showed upregulation of activation markers indicative of antigen presentation, a phenomenon traditionally not observed in neutrophils. Bulk RNA sequencing also reveals a strong emphasis on neutrophil activation, with upregulation of the activation and recruitment marker CXCL1. Conclusion Our finding suggests that myeloid cells in the TME retain the ability to respond to acute stimuli by upregulating antigen presentation markers. Through CXCL1 upregulation, microplastics activate inflammation responses in myeloid cells, particularly neutrophils. We conclude that microplastics could induce myeloid activation and provide novel therapeutic insight into brain tumor biology. Funding Source N/A Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)