Tumour-infiltrating microplastics disrupt the JAK-STAT-microbiota axis to promote immunotherapy resistance in colorectal cancer

Microplastics are pervasive global environmental pollutants. While their potential health impacts are acknowledged, their link to cancer remains unclear. The colorectum is the primary microplastics absorption site and further exploration of the effects of microplastics on colorectal cancer progression and immunotherapy efficacy are warranted. In this study, microplastics were isolated from colorectal cancer tumour tissues and blood, and their properties were examined. microplastics worsened colorectal cancer severity and promoted immunotherapy resistance in animal models. Moreover, microplastics uptake inhibited the JAK-STAT pathway; downregulated IFN-γ, CXCL9, CXCL11, B2m, and H2-K1 expression; decreased CD8+ and CD4+ T-cell infiltration; and increased tumour resistance to immunotherapy. Microplastics also triggered gut microbiota dysbiosis, significantly contributing to colorectal cancer immunotherapy resistance. Microplastics play an important role in colorectal cancer immunotherapy resistance by altering the tumour immune microenvironment and represent a novel target in colorectal cancer immunotherapy, especially amid increasing microplastics pollution.