Combination cancer immunotherapies: Emerging treatment strategies adapted to the tumor microenvironment

Kirchhammer, Nicole; Trefny, Marcel P.; Maur, Priska Auf der; Läubli, Heinz; Zippelius, Alfred

doi:10.1126/scitranslmed.abo3605

Cited by 100 publications

(62 citation statements)

References 74 publications

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“…Furthermore, inhibition or resistance to ferroptosis in vivo emaciates the synergy between immunotherapy and radiation therapy ( 99 ). Major immunosuppressive mechanisms in the tumor microenvironment include high PD-L1 expression and regulatory T cell infiltration ( 100 , 101 ). Radiation can target PD-L1-expressing cells and regulatory T cells ( 102 , 103 ).…”

Section: Ferroptosis In Antitumor Immunitymentioning

confidence: 99%

Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors

et al. 2023

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Low response rate and treatment resistance are frequent problems in the immunotherapy of tumors, resulting in the unsatisfactory therapeutic effects. Ferroptosis is a form of cell death characterized by the accumulation of lipid peroxides. In recent years, it has been found that ferroptosis may be related to the treatment of cancer. Various immune cells (including macrophages and CD8+ T cells) can induce ferroptosis of tumor cells, and synergistically enhance the anti-tumor immune effects. However, the mechanisms are different for each cell types. DAMP released in vitro by cancer cells undergoing ferroptosis lead to the maturation of dendritic cells, cross-induction of CD8+ T cells, IFN-γ production and M1 macrophage production. Thus, it activates the adaptability of the tumor microenvironment and forms positive feedback of the immune response. It suggests that induction of ferroptosis may contribute to reducing resistance of cancer immunotherapy and has great potential in cancer therapy. Further research into the link between ferroptosis and tumor immunotherapy may offer hope for those cancers that are difficult to treat. In this review, we focus on the role of ferroptosis in tumor immunotherapy, explore the role of ferroptosis in various immune cells, and discuss potential applications of ferroptosis in tumor immunotherapy.

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Section: Ferroptosis In Antitumor Immunitymentioning

confidence: 99%

Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors

et al. 2023

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“…Recent advancements in cancer immunology have shifted the paradigm of cancer treatment and has become one of the most prominent therapeutics for human cancers. This breakthrough has prolonged the survival of patients with relapsed or refractory metastatic cancers; however, only a subset of patients display favorable responses and most patients with immunologically cold solid tumors do not respond [ 46 , 47 ]. Emerging evidence has demonstrated that productive antitumor immune response is regulated in multiple cell types of TME and at an extraordinary level of orchestration of an array of coordinated biological processes, such as epigenetic modifications and metabolic reprograming.…”

Section: Arid1a-deficiency: An Immune-metabolic Vulnerabilitymentioning

confidence: 99%

“…Despite the overall impressive clinical effects of ICB in cancer treatment, not all patients respond to immunotherapy. Therefore, there is a substantial and unmet medical need for the development of biomarkers that could predict the response of individual patients to immunotherapeutic agents [ 46 , 47 ]. Recent findings that ARID1A deficiency is related to sensitivity to ICB therapy in multiple cancer types have paved the way of harnessing ARID1A as a novel target for cancer immunotherapy [ 11 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ].…”

Section: Arid1a-deficiency: An Immune-metabolic Vulnerabilitymentioning

confidence: 99%

Targeting ARID1A-Deficient Cancers: An Immune-Metabolic Perspective

Lebedev

Kousar

Patrick

et al. 2023

Cells

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Epigenetic remodeling and metabolic reprogramming, two well-known cancer hallmarks, are highly intertwined. In addition to their abilities to confer cancer cell growth advantage, these alterations play a critical role in dynamically shaping the tumor microenvironment and antitumor immunity. Recent studies point toward the interplay between epigenetic regulation and metabolic rewiring as a potentially targetable Achilles’ heel in cancer. In this review, we explore the key metabolic mechanisms that underpin the immunomodulatory role of AT-rich interaction domain 1A (ARID1A), the most frequently mutated epigenetic regulator across human cancers. We will summarize the recent advances in targeting ARID1A-deficient cancers by harnessing immune-metabolic vulnerability elicited by ARID1A deficiency to stimulate antitumor immune response, and ultimately, to improve patient outcome.

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“…In addition, TME is critically involved in clinical intervention and changes treatment outcomes. Modulation of TME is useful for fine-tuning of therapy strategies (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

et al. 2023

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The tumor microenvironment (TME) is the tumor surrounding environment, which is critical for tumor development and progression. TME is also involved in clinical intervention and treatment outcomes. Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Evidence has demonstrated that the expression of PD-1/PD-L1 is associated with clinical response to anti-PD-1/PD-L1 therapy in cancer patients. It is important to discuss the regulatory machinery how PD-1/PD-L1 protein is finely regulated in tumor cells. In recent years, studies have demonstrated that PD-1/PD-L1 expression was governed by various E3 ubiquitin ligases in TME, contributing to resistance of anti-PD-1/PD-L1 therapy in human cancers. In this review, we will discuss the role and molecular mechanisms of E3 ligases-mediated regulation of PD-1 and PD-L1 in TME. Moreover, we will describe how E3 ligases-involved PD-1/PD-L1 regulation alters anti-PD-1/PD-L1 efficacy. Altogether, targeting E3 ubiquitin ligases to control the PD-1/PD-L1 protein levels could be a potential strategy to potentiate immunotherapeutic effects in cancer patients.

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Combination cancer immunotherapies: Emerging treatment strategies adapted to the tumor microenvironment

Cited by 100 publications

References 74 publications

Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors

Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors

Targeting ARID1A-Deficient Cancers: An Immune-Metabolic Perspective

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

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