Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma

Wu, Jiangchao; Wang, Xun; Chen, Li; Wang, Jianbo; Zhang, Junlei; Tang, Jianghui; Ji, Yongtao; Song, Jinyuan; Wang, Lin; Zhao, Yaxing; Zhang, Hui; Li, Taohong; Sheng, Jianpeng; Chen, Dong; Zhang, Qi; Liang, Tingbo

doi:10.1016/j.bioactmat.2022.05.022

Cited by 12 publications

(17 citation statements)

References 43 publications

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“…Additional oxygen not only alleviates hypoxia, but can also induce inflammation; therefore, the right dosage reaching the target is difficult to obtain. Moreover, respiratory oxygen application efforts are made to enclose oxygen in microcapsules, which was shown to improve immune checkpoint blockades in pre-clinical studies [ 50 ]. This might also be an issue, especially in the context of anti-cancer drugs such as doxorubicin and angiogenesis inhibitors, where inflammation and endotheliotoxicity are significant risks [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium

et al. 2022

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Patients presenting with insufficient tissue oxygenation and impaired lung function as in acute respiratory distress syndrome (ARDS) frequently require mechanical ventilation with supplemental oxygen. Despite the lung being used to experiencing the highest partial pressure of oxygen during healthy breathing, the organ is susceptible to oxygen-induced injury at supraphysiological concentrations. Hyperoxia-induced lung injury (HALI) has been regarded as a second hit to pre-existing lung injury and ventilator-induced lung injury (VILI) attributed to oxidative stress. The injured lung has a tendency to form atelectasis, a cyclic collapse and reopening of alveoli. The affected lung areas experience oxygen conditions that oscillate between hyperoxia and hypoxia rather than remaining in a constant hyperoxic state. Mechanisms of HALI have been investigated in many animal models previously. These studies provided insights into the effects of hyperoxia on the whole organism. However, cell type-specific responses have not been dissected in detail, but are necessary for a complete mechanistic understanding of ongoing pathological processes. In our study, we investigated the effects of constant and intermittent hyperoxia on the lung endothelium from a mouse by an in vitro proteomic approach. We demonstrate that these oxygen conditions have characteristic effects on the pulmonary endothelial proteome that underlie the physiological (patho)mechanisms.

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Section: Discussionmentioning

confidence: 99%

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium

et al. 2022

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“…394 To overcome this challenge, nano-and bio-based technologies have been used to carry oxygen generators to generate enough oxygen in the target cancer such as pancreatic ductal adenocarcinoma, colorectal cancer, fibrosarcoma, melanoma, etc., which aids in drug delivery and significantly improves the effectiveness of chemotherapy, radiotherapy as well as immunotherapy. 281,[395][396][397][398] Moreover, the reoxygenation process generates large amounts of ROS, which results in DNA damage, contributing to cancer cell death. 65,399 However, the damage this brings to the surrounding normal cells is a matter of concern.…”

Section: Hypoxia-mediated Therapymentioning

confidence: 99%

“…235,281 Pro-oxidants can also be used to increase oxygen levels in the TME. Wu et al 396 developed nanoparticle-stabilized oxygen microcapsules that could be precisely targeted to pancreatic ductal adenocarcinoma (PDAC), improving hypoxia and significantly increasing the efficacy of anti-PD-1 antibodies against PDAC. Treatment with oxygen microcapsules combined with anti-PD-1 antibodies alleviates TAM infiltration, polarizes macrophages from the pro-cancer M2 phenotype to the anticancer M1 phenotype, and increases the proportion of TME Th1 cells and CTLs to enhance anti-cancer immune effects.…”

Section: Hypoxia and Immunotherapymentioning

confidence: 99%

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Zhou

Han

et al. 2023

Sig Transduct Target Ther

236

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Having a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.

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“…Hypoxia can induce and maintain an immunosuppressive TME and activate PSCs to mediate fibrosis [ 60 ]. Therapeutic strategies targeting optimized hypoxia have shown synergistic improvements in immunotherapy in the preclinical studies for pancreatic cancer [ 61 , 62 ]. In a phase I clinical trial, evofosfamide (prodrug that alleviates hypoxia) combined with ipilimumab was tested in advanced solid malignancies.…”

Section: Status and Dilemma Of Immunotherapy For Pdacmentioning

confidence: 99%

“…Recently, microcapsules for oxygen delivery were proposed. Here, the oxygen microcapsules provided a stable oxygen delivery deep into the tumor, reversed hypoxia in the TME, and improved the performance of ICB in PDAC [ 62 ].…”

Section: Nanoparticle-based Therapeutic Strategies For Enhanced Pdac ...mentioning

confidence: 99%

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy

2022

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Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applications in improving drug delivery and reversing the immunosuppressive TME for PDAC. Therefore, nanomaterial-based therapeutic approaches are expected to enhance the effectiveness of immunotherapy and improve prognosis of patients with PDAC. Here, we outline the status and dilemma of PDAC immunotherapy, and summarize the latest advances in nanoparticle-based treatment strategies to enhance the efficacy of PDAC immunotherapy.

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Oxygen microcapsules improve immune checkpoint blockade by ameliorating hypoxia condition in pancreatic ductal adenocarcinoma

Cited by 12 publications

References 43 publications

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium

Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy

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