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.

中文翻译：

---

巨噬细胞膜包被的纳米吉西他滨促进淋巴细胞浸润并协同抗PD-L1恢复杀瘤功能

实体瘤中有限的淋巴细胞浸润和杀瘤功能的耗尽仍然是癌症免疫治疗的巨大障碍。在此，我们设计了一种巨噬细胞膜包被的纳米吉西他滨系统 (MNGs) 来促进淋巴细胞浸润，然后协同抗程序性死亡配体 1 (antiPD-L1) 来重振衰竭的淋巴细胞。MNGs 表现出有效的肿瘤内渗透和反应性药物释放能力，显着消除多功能免疫抑制细胞，并促进淋巴细胞浸润到肿瘤的癌细胞区域，但超过 50% 的浸润淋巴细胞处于耗尽状态。与 MNG 单一疗法相比，MNGs + antiPD-L1 组合产生的衰竭 CD3 ⁺ CD8 ^{+减少了 31.77% 和 30.63%}T 细胞和自然杀伤 (NK) 细胞以及干扰素-γ (IFN-γ) 阳性亚型分别增加 2.83 倍和 3.17 倍，从而在多种肿瘤模型中产生相当大的治疗益处。因此，MNGs 提供了一种令人鼓舞的策略来促进淋巴细胞浸润并协同抗 PD-L1 以恢复其用于癌症免疫治疗的肿瘤杀伤功能。