Generation of durable tumor-specific immune response without isolation and expansion of dendritic cells or T cells ex vivo remains a challenge. In this study, we investigated the impact of nanoparticle-mediated photothermolysis in combination with checkpoint inhibition on the induction of systemic antitumor immunity. Photothermolysis based on near-infrared light-absorbing copper sulfide nanoparticles and 15-ns laser pulses combined with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) increased tumor infiltration by antigen-presenting cells and CD8-positive T lymphocytes in the B16-OVA mouse model. Moreover, combined photothermolysis, polymeric conjugate of the Toll-like receptor 9 agonist CpG, and αPD-1 significantly prolonged mouse survival after re-inoculation of tumor cells at a distant site compared to individual treatments alone in the poorly immunogenic syngeneic ID8-ip1-Luc ovarian tumor model. Thus, photothermolysis is a promising interventional technique that synergizes with Toll-like receptor 9 agonists and immune checkpoint inhibitors to enhance the abscopal effect in tumors.

中文翻译：

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通过基于纳米粒子的光热解和抗PD-1检查点抑制的组合，诱导小鼠抗肿瘤免疫。

没有离体的树突状细胞或T细胞的分离和扩增而产生持久的肿瘤特异性免疫应答仍然是一个挑战。在这项研究中，我们调查了纳米粒子介导的光热解结合检查点抑制对全身抗肿瘤免疫诱导的影响。基于近红外吸收光的硫化铜纳米粒子和15 ns激光脉冲与免疫检查点抑制剂抗PD-1抗体（αPD-1）结合的光热解增加了抗原呈递细胞和CD8阳性T淋巴细胞对肿瘤的浸润。 B16-OVA鼠标模型。此外，结合光热解法，Toll样受体9激动剂CpG的聚合共轭物，与免疫原性差的同基因ID8-ip1-Luc卵巢肿瘤模型中的单独治疗相比，αPD-1和αPD-1在远处重新接种肿瘤细胞后可显着延长小鼠存活。因此，光热解是一种有前途的介入技术，可与Toll样受体9激动剂和免疫检查点抑制剂协同作用，以增强肿瘤的抽象作用。