Combining local cryoablation with PD-L1 blockade synergistically eradicates established murine lung cancer by modulating mitochondrial in PD-1+CD8+ T cell

Zhai, Jia-Wei; Lv, Lei-lei; Wu, Jia-juan; Zhang, Yao-xin; Shen, Yu; Qu, Qiu-xia; Chen, Cheng

doi:10.1016/j.imlet.2023.10.002

Immunology Letters

2023

DOI: 10.1016/j.imlet.2023.10.002

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Combining local cryoablation with PD-L1 blockade synergistically eradicates established murine lung cancer by modulating mitochondrial in PD-1+CD8+ T cell

Jia-Wei Zhai,

Lei-lei Lv,

Jia-juan Wu

et al.

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2024

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Cited by 3 publications

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Reversal of T-cell exhaustion: Mechanisms and synergistic approaches

Hu,

Zhang,

Shi

et al. 2024

International Immunopharmacology

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Reversal of T-cell exhaustion: Mechanisms and synergistic approaches

Hu,

Zhang,

Shi

et al. 2024

International Immunopharmacology

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CRYOVATE: A Pilot Study of Lung Cancer Cryoactivation in Combination With Immunotherapy in Advanced NSCLC

Desilets,

Pinheiro,

Belkaid

et al. 2024

JTO Clinical and Research Reports

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Cryo-Nanocatalyst Enhances Therapeutic Efficacy of Cryo-Immunotherapy through Necroptosis and Local Delivery of Programmed Death-Ligand 1 Inhibitors

Lee,

Ko,

Avritscher

et al. 2024

ACS Nano

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Combining cryoablation and immunotherapy presents a promising approach to revert immunosuppressive responses to solid tumors. However, challenges such as postablated residual tumors and insufficient immune activity contribute to recurrence after cryo-immunotherapy. Herein, we investigated metallic supra-structured cryo-nanocatalyst (MSCN), which features numerous ice nucleation sites and interspace loading of therapeutic agents. MSCN elevates the freezing point and enhances ice nucleation, facilitating effective ice formation during cryotreatment. MSCN-loaded tumor cells showed a 2-fold increase in cryo-cytotoxicity and undergo osmotic-related cell damage, primarily necroptosis rather than other regulated cell death mechanisms. In prostate cancer models, RNA sequencing reveals that MSCN-cryoablation promoted antitumor inflammatory pathways, including necroptosis, compared to cryoablation alone. Additionally, following programmed death-ligand 1 (PD-L1) upregulation postcryoablation, synergistic effects with PD-L1 blockade were confirmed. Given the interspace of MSCN for aPD-L1 loading, we compared the intratumoral delivery of PD-L1 blockade against systemic injection. Enhanced necrosis and necroptosis from MSCNcryoablation and PD-L1 blockade effectively eradicated tumors and triggered antitumor and memory immune responses locally and systemically. Lastly, a spatial landscape of tumor-infiltrating immune cells was analyzed to gain insight into heterogeneous tumor responses, leading to the limitations of conventional focal ablation techniques. Our findings highlight the potential of advanced cryo-immunotherapy using cryo-nanocatalysis to promote ice formation and necroptosis, stimulating antitumor immunogenic responses.

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Combining local cryoablation with PD-L1 blockade synergistically eradicates established murine lung cancer by modulating mitochondrial in PD-1+CD8+ T cell

Cited by 3 publications

References 38 publications

Reversal of T-cell exhaustion: Mechanisms and synergistic approaches

Reversal of T-cell exhaustion: Mechanisms and synergistic approaches

CRYOVATE: A Pilot Study of Lung Cancer Cryoactivation in Combination With Immunotherapy in Advanced NSCLC

Cryo-Nanocatalyst Enhances Therapeutic Efficacy of Cryo-Immunotherapy through Necroptosis and Local Delivery of Programmed Death-Ligand 1 Inhibitors

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