巨噬细胞膜包被的纳米吉西他滨促进淋巴细胞浸润并与抗 PD-L1 协同恢复杀肿瘤功能

The limited lymphocyte infiltration and exhaustion of tumoricidal functions in solid tumors remain a formidable obstacle to cancer immunotherapy.

Herein, we designed a macrophage membrane-coated nano-gemcitabine system (MNGs) to promote lymphocyte infiltration and then synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes. MNGs exhibited effective intratumor-permeating and responsive drug-releasing capacity, produced notable elimination of versatile immunosuppressive cells, and promoted lymphocyte infiltration into cancer cell regions in tumors, but over 50% of these infiltrated lymphocytes were in the exhausted state.

Compared with MNG monotherapy, the MNGs+antiPD-L1 combination produced 31. 77% and 30. 63% reduction of exhausted CD3 + CD8 + T cells and natural killer (NK) cells and 2. 83- and 3. 17-fold increases of interferon-γ (IFN-γ)-positive subtypes, respectively, thereby resulting in considerable therapeutic benefits in several tumor models.

Thus, MNGs provide an encouraging strategy to promote lymphocyte infiltration and synergize antiPD-L1 to restore their tumoricidal function for cancer immunotherapy.