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The exhaustion of T cells within the tumor immune microenvironment (TIME) can weaken the efficacy of radioimmunotherapy. This study demonstrates that X-ray radiotherapy can induce imbalances in arginine metabolism and upregulation of PD-L1 in the tumor microenvironment (TME), inhibit T cell metabolism, promote the expansion of PD-1+TIM-3+ exhausted T cells, thereby promoting immunosuppression. Therefore, we designed a biomimetic hybrid immunomodulator (arg/Bnb-L), which uses engineered BL-21 bacterial membranes to display PD-L1 nanobodies and fuses them with l-arginine-loaded liposomes. This nanoplatform simultaneously blocks PD-1/PD-L1 immune checkpoint signals, restores T cell metabolic activity, and promotes the maturation of dendritic cells. In mouse tumor models, Arg/Bnb-L combined with radiotherapy significantly enhances CD8+ T cell infiltration, reduces the population of exhausted T cells, maintains the function of cytotoxic T lymphocytes, and inhibits tumor progression and metastasis. Our research elucidates the dual mechanisms by which radiotherapy induces immunosuppression and provides a promising strategy for enhancing the efficacy of radioimmunotherapy by targeting metabolism and immunoreprogramming. This study was published in ACS Nano under the title "Bacteria-Derived Nanobody-Decorated Nanoplatform Restores T Cell Immunity Post-Radiotherapy".
Reference: DOI: 10.1021/acsnano.6c00839
