基于免疫检查点抑制剂的癌症免疫疗法已显示出作为临床潜在治疗方法的前景。有报道抗PD-L1联合顺铂治疗可提高抗肿瘤效果。然而，由于胰腺癌（PC）中肿瘤基质丰富，阻碍了顺铂和抗PD-L1渗透到肿瘤区域，从而阻碍了PC治疗的有效性，因此治疗结果受到限制。本研究构建了纳米载体介导的透明质酸酶和顺铂共递送系统，能够降解基质，促进顺铂和抗PD-L1渗透肿瘤基质进入肿瘤深部，从而有效抑制PC。当将顺铂纳米载体系统BPEI-SS-Pt/HAase@CaP（BSP/H@CaP）与免疫检查点抑制剂联合来克服PC的不良治疗效果时，结果表明BSP/H@CaP联合的治疗效果抗PD-L1组优于BSP/H@CaP组和单抗PD-L1组。由于基质正在降解，大量的 BPEI-SS-Pt 和抗 PD-L1 可以进入肿瘤基质并到达肿瘤内部深处进行免疫刺激，从而对 PC 进行协同增强的化疗和免疫治疗。上述联合疗法可用于临床转化，以克服富含基质的 PC 的治疗耐药性。版权所有 © 2024 Elsevier Ltd. 保留所有权利。

Immune checkpoint inhibitor-based cancer immunotherapy has shown promise as a potential treatment in the clinic. It has been reported that anti-PD-L1 combined with cisplatin treatment can improve the antitumor effect. However, the therapeutic outcome is limited due to the abundance of tumor stroma in pancreatic cancer (PC), which prevented the penetration of cisplatin and anti-PD-L1 into tumor regions, thus impeding the effectiveness in the treatment of PC. In this study, a nanocarrier-mediated codelivery system of hyaluronidase and cisplatin was constructed, which can degrade the stroma and promote cisplatin and anti-PD-L1 to penetrate the tumor stroma into the deep tumor, so as to suppress PC effectively. When combined the cisplatin nanocarrier system BPEI-SS-Pt/HAase@CaP (BSP/H@CaP) with an immune checkpoint inhibitor to overcome the poor therapeutic outcome of PC, the results indicated that the therapeutic effect of BSP/H@CaP combined with anti-PD-L1 was better than that of BSP/H@CaP and single anti-PD-L1 group. Because the stroma is degrading, a higher amount of BPEI-SS-Pt and anti-PD-L1 can enter the tumor stroma and reach the inner depths of the tumor for immune stimulation, leading to a synergistically augmented chemotherapy and immunotherapy for PC. The above combination therapy is useful for clinical translation to overcome the treatment resistance of matrix-rich PC.Copyright © 2024 Elsevier Ltd. All rights reserved.