Nanoplastics impair antitumor NK and CD8⁺ T cell cytotoxicity and antiviral B cell antibody responses to SARS-CoV-2.

Nanoplastics are pervasive environmental contaminants that continuously expose humans and accumulate in multiple organs. Increasing evidence associates NPs with adverse health effects, including inflammation and carcinogenesis, yet their impact on human innate and adaptive immunity remains poorly understood. This knowledge gap is particularly relevant for diseases treated with therapies that modulate immune responses. Here, we investigated the effects of NP exposure on major subsets of human peripheral lymphocytes, essential for antitumor and antiviral defense while preserving immune tolerance. Peripheral blood mononuclear cells from healthy donors were exposed to oxidized and plasma-exposed NPs, which acquired a stable protein corona. NP exposure induced a time-dependent increase in immune cell interactions and resulted in reduced activation and functionality of CD4⁺ and CD8⁺ T cells, B cells, and natural killer cells. T lymphocytes displayed impaired tumor antigen-specific responses, while natural killer cells showed decreased tumor cell-killing capacity. Notably, B cells internalized NPs, leading to reduced ability to generate antibodies against SARS-CoV-2. Overall, these findings demonstrate that NPs compromise both innate and adaptive immune functions, weakening antiviral and antitumor responses. Our results highlight potential risks associated with NP exposure for susceptibility to infections and cancer as well as immune-based therapy efficacy.