T lymphocyte-derived immunogenic hybrid nanovesicles for immunosuppression reversion and boosted photothermal immunotherapy

Photothermal therapy (PTT) can mediate the immunogenic cell death (ICD) of tumors through photothermal transformation, thus releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) to stimulate the maturation of dendritic cells (DCs) and elicit the immune response against tumors. However, PTT-mediated upregulation of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) will cause the immune evasion of tumor cells and thus increases the immunosuppression of cytotoxic T lymphocytes (CTLs), resulting in restricted photothermal immune activation. Taking advantage of the high expression of programmed cell death protein 1 (PD-1) in T lymphocytes, we develop an immunogenic photothermal hybrid nanovesicle to reverse immunosuppression and enhance PTT-induced ICD. The hybrid vesicle (TMVL-I) is constructed by phospholipid bilayer fusion of T cell-derived membrane vesicle (TMV) with high PD-1 expression and the indocyanine green (ICG)-loaded thermosensitive liposome (L-I). TMVL-Is bind to the tumor cells with PTT-induced upregulation of PD-L1, effectively blocking the PD-1/PD-L1 pathway between CTLs and tumor cells, thus reversing PD-L1-mediated tumor immunosuppression and intensifying photothermal-induced ICD effects. These processes significantly induce the maturation of DCs and enhance the infiltration of CTLs into both primary and distal tumors and the activation of spleen CTLs, strongly inhibiting the growth of B16 xenograft tumors and greatly improving the survival rate of B16 xenograft mice. This work provides a feasible strategy for immunosuppressive microenvironment reprogramming-based combination therapy.