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Black phosphorus-based photothermal therapy with aCD47-mediated immune checkpoint blockade for enhanced cancer immunotherapy.

ABSTRACT: Here, we describe a combination strategy of black phosphorus (BP)-based photothermal therapy together with anti-CD47 antibody (aCD47)-based immunotherapy to synergistically enhance cancer treatment. Tumour resistance to immune checkpoint blockades in most cancers due to immune escape from host surveillance, along with the initiation of metastasis through immunosuppressive cells in the tumour microenvironment, remains a significant challenge for cancer immunotherapy. aCD47, an agent for CD47/SIRPα axis blockade, induces modest phagocytic activity and a low response rate for monotherapy, resulting in failures in clinical trials. We showed that BP-mediated ablation of tumours through photothermal effects could serve as an effective strategy for specific immunological stimulation, improving the inherently poor immunogenicity of tumours, which is particularly useful for enhancing cancer immunotherapy. BP in combination with aCD47 blockade activates both innate and adaptive immunities and promotes local and systemic anticancer immune responses, thus offering a synergistically enhanced effect in suppression of tumour progression and in inducing abscopal effects for inhibition of metastatic cancers. Our combination strategy provides a promising platform in which photothermal agents could help to enhance the therapeutic efficacy of immunotherapy.

SUBMITTER: Xie Z

PROVIDER: S-EPMC7492464 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Black phosphorus-based photothermal therapy with aCD47-mediated immune checkpoint blockade for enhanced cancer immunotherapy.

Xie Zhongjian Z Peng Minhua M Lu Ruitao R Meng Xiangying X Liang Weiyuan W Li Zhongjun Z Qiu Meng M Zhang Bin B Nie Guohui G Xie Ni N Zhang Han H Prasad Paras N PN

Light, science & applications 20200915

Here, we describe a combination strategy of black phosphorus (BP)-based photothermal therapy together with anti-CD47 antibody (aCD47)-based immunotherapy to synergistically enhance cancer treatment. Tumour resistance to immune checkpoint blockades in most cancers due to immune escape from host surveillance, along with the initiation of metastasis through immunosuppressive cells in the tumour microenvironment, remains a significant challenge for cancer immunotherapy. aCD47, an agent for CD47/SIRP ...[more]

PMID: 33014356

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Project description:Immunotherapy has emerged as a hotspot for cancer treatment. However, the response rate of monotherapy remains relatively low in clinical settings. Photothermal therapy (PTT), which employs light energy to ablate tumors, can also activate tumor-specific immune responses. This effect has been attributed in several studies to the release of damage-associated molecular patterns (DAMPs) triggered by mitochondrial injury. We propose that mitochondria-targeted PTT may better synergize with immunotherapy. Herein, we constructed a multifunctional nanoplatform that enables mitochondria-targeted photothermal-chemodynamic combination therapy by conjugating indocyanine green-thiol (ICG-SH) and mercaptoethyl-triphenylphosphonium (TPP-SH) onto polyvinyl pyrrolidone (PVP)-coated gold-copper nanoparticles (AIT). Upon near-infrared light (NIR) irradiation, AIT ablates cancer cells and amplifies the effect of chemodynamic therapy (CDT), thereby inducing apoptosis in the tumor. The combination of CDT and PTT promotes immunogenic cell death, which could synergize with checkpoint blockade immunotherapy. In a bilateral mouse colon cancer model, we observed complete eradication of light-irradiated primary tumors and significant inhibition of distant untreated tumors in the group treated with AIT plus anti-PD-1 (αPD-1). We found a significant increase in serum levels of pro-inflammatory factors, including interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), following PTT/CDT/immunotherapy treatment, suggesting effective activation of the immune response. The enhanced immunogenicity caused by AIT with αPD-1 treatment resulted in efficient antigen presentation, as indicated by the increased infiltration of dendritic cells (DCs) into the tumor-draining lymph nodes (LNs). We also observed enhanced infiltration of CD8+ T cells in distant tumors in the AIT with αPD-1 group compared to αPD-1 alone. Hence, mitochondria-targeting represents an effective strategy to potentiate the combination of photothermal, chemodynamic, and immune checkpoint blockade therapies for the treatment of metastatic cancer.

Dataset Information

Black phosphorus-based photothermal therapy with aCD47-mediated immune checkpoint blockade for enhanced cancer immunotherapy.

Publications

Black phosphorus-based photothermal therapy with aCD47-mediated immune checkpoint blockade for enhanced cancer immunotherapy.

Similar Datasets

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