Improving the synergistic combination of programmed death‐1/programmed death ligand‐1 blockade and radiotherapy by targeting the hypoxic tumour microenvironment

Mudassar, Faiqa; Shen, Han; Cook, Kristina M.; Hau, Eric

doi:10.1111/1754-9485.13416

Cited by 3 publications

(3 citation statements)

References 166 publications

(340 reference statements)

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“…Hypoxia is a hallmark of solid tumors that reduces their susceptibility to radiation therapy and is a driver of immunotherapy resistance (145). Given the enormous benefits of targeting hypoxia for RT and immunotherapy, a number of regiments have been developed to ameliorate hypoxia to increase the efficacy of radiotherapy combined with immunotherapy, including increasing oxygen supply to tumors, inhibiting mitochondrial oxidative phosphorylation (OXPHOS), inhibiting HIF activity (146).…”

Section: Ameliorate Hypoxia To Induce Oxidative Stress To Enhance Rad...mentioning

confidence: 99%

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy

Zheng

Bao

et al. 2023

Front. Immunol.

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Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to the death of tumor cells. OS not only causes apoptosis, autophagy and ferroptosis, but also affects tumor immune response. The combination of RT and immunotherapy has revolutionized the management of various cancers. In this process, OS caused by ROS plays a critical role. Specifically, RT-induced ROS can promote the release of tumor-associated antigens (TAAs), regulate the infiltration and differentiation of immune cells, manipulate the expression of immune checkpoints, and change the tumor immune microenvironment (TME). In this review, we briefly summarize several ways in which IR induces tumor cell death and discuss the interrelationship between RT-induced OS and antitumor immunity, with a focus on the interaction of ferroptosis with immunogenic death. We also summarize the potential mechanisms by which ROS regulates immune checkpoint expression, immune cells activity, and differentiation. In addition, we conclude the therapeutic opportunity improving radiotherapy in combination with immunotherapy by regulating OS, which may be beneficial for clinical treatment.

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Section: Ameliorate Hypoxia To Induce Oxidative Stress To Enhance Rad...mentioning

confidence: 99%

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy

Zheng

Bao

et al. 2023

Front. Immunol.

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“…The mechanism of this improvement was further studied, and it was found that CD8+ T lymphocytes were increased in the tumor site, M1/M2 macrophage ratios were increased, and immunosuppressive myeloid cells were decreased in the combination treatment in both primary and secondary metastatic tumor sites. They also found that tumor hypoxia was somewhat relieved by utilizing these NPs, which has been identified as a limiting factor for radio-immunotherapy/abscopal responses (Mudassar et al, 2022). Of note, MnO 2 NPs have previously been used to catalyze the breakdown of hydrogen peroxide into molecular oxygen, which increases the efficacy of RT by increasing the production of tumoricidal ROS and relieving tumor hypoxia (Prasad et al, 2014).…”

Section: Considerations For the Preclinical Study Of Combining Icis W...mentioning

confidence: 99%

Nanotechnology‐enhanced radiotherapy and the abscopal effect: Current status and challenges of nanomaterial‐based radio‐immunotherapy

Viswanath,

Park,

Misra

et al. 2023

WIREs Nanomed Nanobiotechnol

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Rare but consistent reports of abscopal remission in patients challenge the notion that radiotherapy (RT) is a local treatment; radiation‐induced cancer cell death can trigger activation and recruitment of dendritic cells to the primary tumor site, which subsequently initiates systemic immune responses against metastatic lesions. Although this abscopal effect was initially considered an anomaly, combining RT with immune checkpoint inhibitor therapies has been shown to greatly improve the incidence of abscopal responses via modulation of the immunosuppressive tumor microenvironment. Preclinical studies have demonstrated that nanomaterials can further improve the reliability and potency of the abscopal effect for various different types of cancer by (1) altering the cell death process to be more immunogenic, (2) facilitating the capture and transfer of tumor antigens from the site of cancer cell death to antigen‐presenting cells, and (3) co‐delivering immune checkpoint inhibitors along with radio‐enhancing agents. Several unanswered questions remain concerning the exact mechanisms of action for nanomaterial‐enhanced RT and for its combination with immune checkpoint inhibition and other immunostimulatory treatments in clinically relevant settings. The purpose of this article is to summarize key recent developments in this field and also highlight knowledge gaps that exist in this field. An improved mechanistic understanding will be critical for clinical translation of nanomaterials for advanced radio‐immunotherapy.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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“…Due to the hypoxic tumour microenvironment and amplified PD-L1 expression, the response to RT is impaired. Recent promising experimental studies have focused on targeting the hypoxic tumour environment as well as improved anti-PD-L1 efficacy with specifically developed nanoparticles to improve the efficacy of (immune-RT [77,78]. Other techniques to improve the efficacy of preoperative RT are being investigated in phase I/II trials, such as dose intensification only to the posterior wall for high-risk margins of RPS through "dose painting" with proton or photon IMRT (NCT01659203) [79].…”

Section: Perioperative Radiotherapymentioning

confidence: 99%

Retroperitoneal Soft Tissue Sarcoma: Emerging Therapeutic Strategies

de Bree,

Michelakis,

Heretis

et al. 2023

Cancers

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Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is usually unfeasible in RPS due to its large size, indistinct tumour borders, anatomical constraints and the thinness of the overlying peritoneum. Local recurrence is the leading cause of death for low-grade RPS, whereas high-grade tumours are prone to distant metastases. In recent decades, the role of emerging therapeutic strategies, such as more extended surgery and (neo)adjuvant treatments to improve oncological outcome in primary localised RPS, has been extensively investigated. In this review, the recent data on the evolving multidisciplinary management of primary localised RPS are comprehensively discussed. The heterogeneity of RPS, with their different histological subtypes and biological behaviour, renders a standard therapeutic ‘one-size-fits-all’ approach inappropriate, and treatment should be modified according to histological type and malignancy grade. There is sufficient evidence that frontline extended surgery with compartmental resection including all ipsilateral retroperitoneal fat and liberal en bloc resection of adjacent organs and structures, even if they are not macroscopically involved, increases local tumour control in low-grade sarcoma and liposarcoma, but not in leiomyosarcoma for which complete macroscopic resection seems sufficient. Additionally, preoperative radiotherapy is not indicated for all RPSs, but seems to be beneficial in well-differentiated liposarcoma and grade I/II dedifferentiated liposarcoma, and probably in solitary fibrous tumour. Whether neoadjuvant chemotherapy is of benefit in high-grade RPS remains unclear from retrospective data and is subject of the ongoing randomised STRASS 2 trial, from which the results are eagerly awaited. Personalised, histology-tailored multimodality treatment is promising and will likely further evolve as our understanding of the molecular and genetic characteristics within RPS improves.

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Improving the synergistic combination of programmed death‐1/programmed death ligand‐1 blockade and radiotherapy by targeting the hypoxic tumour microenvironment

Cited by 3 publications

References 166 publications

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy

Nanotechnology‐enhanced radiotherapy and the abscopal effect: Current status and challenges of nanomaterial‐based radio‐immunotherapy

Retroperitoneal Soft Tissue Sarcoma: Emerging Therapeutic Strategies

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