Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness

Barnestein, Robby; Galland, Loïck; Kalfeist, Laura; Ghiringhelli, François; Ladoire, Sylvain; Limagne, Emeric

doi:10.1080/2162402x.2022.2120676

Cited by 48 publications

(31 citation statements)

References 242 publications

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“…Te notion of a complex tumor environment that promotes tumor growth and metastatic dispersion has replaced the tumor cell-centered perspective of cancer development as a result of the realization of the TME's crucial role in the genesis and progression of cancer [48]. As a result, new TME targets have been found that may assist, guide, and enhance the efects of numerous cancer medicines.…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Mbugua

2022

Bioinorganic Chemistry and Applications

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Solid tumors have a unique tumor microenvironment (TME), which includes hypoxia, low acidity, and high hydrogen peroxide and glutathione (GSH) levels, among others. These unique factors, which offer favourable microenvironments and nourishment for tumor development and spread, also serve as a gateway for specific and successful cancer therapies. A good example is metal peroxide structures which have been synthesized and utilized to enhance oxygen supply and they have shown great promise in the alleviation of hypoxia. In a hypoxic environment, certain oxygen-dependent treatments such as photodynamic therapy and radiotherapy fail to respond and therefore modulating the hypoxic tumor microenvironment has been found to enhance the antitumor impact of certain drugs. Under acidic environments, the hydrogen peroxide produced by the reaction of metal peroxides with water not only induces oxidative stress but also produces additional oxygen. This is achieved since hydrogen peroxide acts as a reactive substrate for molecules such as catalyse enzymes, alleviating tumor hypoxia observed in the tumor microenvironment. Metal ions released in the process can also offer distinct bioactivity in their own right. Metal peroxides used in anticancer therapy are a rapidly evolving field, and there is good evidence that they are a good option for regulating the tumor microenvironment in cancer therapy. In this regard, the synthesis and mechanisms behind the successful application of metal peroxides to specifically target the tumor microenvironment are highlighted in this review. Various characteristics of TME such as angiogenesis, inflammation, hypoxia, acidity levels, and metal ion homeostasis are addressed in this regard, together with certain forms of synergistic combination treatments.

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Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Mbugua

2022

Bioinorganic Chemistry and Applications

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“…Local immune suppression and dysregulation are common features of cancer and are closely associated with tumor metastasis and resistance to therapy. The interaction between cancer and the host immune system is a key factor in determining tumor control or progression (1)(2)(3). Tumor infiltrating leukocytes, particularly monocytes, myeloid derived suppressor cells (MDSCs) and neutrophils create a tumor microenvironment (TME) that is inhospitable to effector cells such as CD4 and CD8 T cells and NK cells (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

2023

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Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers current strategies targeting myeloid suppressor cells in the TME to enhance anti-tumoral immunity, including strategies that target chemokine receptors to deplete selected immune suppressive myeloid cells and relieve the inhibition imposed on the effector arms of adaptive immunity. Remodeling the TME can in turn improve the activity of other immunotherapies such as checkpoint blockade and adoptive T cell therapies in immunologically “cold” tumors. When possible, in this review, we have provided evidence and outcomes from recent or current clinical trials evaluating the effectiveness of the specific strategies used to target myeloid cells in the TME. The review seeks to provide a broad overview of how myeloid cell targeting can become a key foundational approach to an overall strategy for improving tumor responses to immunotherapy.

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“…Given this reliance on the TME, there is an opportunity for antitumor immunotherapies that work by targeting TME components and their signaling pathways (11,12). Although tremendous progress has been made in the past few years, including immune checkpoint inhibitors (13), bispecific antibodies (14) and chimeric antigen receptor (CAR) T cells (15), many studies focusing on elements of the TME have failed to show promising efficacy in patients, particularly with sustainable efficacy (16)(17)(18). Therefore, the development of new immunotherapies may also require consideration of the key transcription regulatory factors involved in multiple components and processes in the TME.…”

Section: Introductionmentioning

confidence: 99%

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

Liang²,

Li³

et al. 2023

Front. Immunol.

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The tumor microenvironment (TME) is implicated in tumorigenesis, chemoresistance, immunotherapy failure and tumor recurrence. Multiple immunosuppressive cells and soluble secreted cytokines together drive and accelerate TME disorders, T cell immunodeficiency and tumor growth. Thus, it is essential to comprehensively understand the TME status, immune cells involved and key transcriptional factors, and extend this knowledge to therapies that target dysfunctional T cells in the TME. Interferon regulatory factor 4 (IRF4) is a unique IRF family member that is not regulated by interferons, instead, is mainly induced upon T-cell receptor signaling, Toll-like receptors and tumor necrosis factor receptors. IRF4 is largely restricted to immune cells and plays critical roles in the differentiation and function of effector cells and immunosuppressive cells, particularly during clonal expansion and the effector function of T cells. However, in a specific biological context, it is also involved in the transcriptional process of T cell exhaustion with its binding partners. Given the multiple effects of IRF4 on immune cells, especially T cells, manipulating IRF4 may be an important therapeutic target for reversing T cell exhaustion and TME disorders, thus promoting anti-tumor immunity. This study reviews the regulatory effects of IRF4 on various immune cells in the TME, and reveals its potential mechanisms, providing a novel direction for clinical immune intervention.

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Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness

Cited by 48 publications

References 242 publications

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

Regulatory effects of IRF4 on immune cells in the tumor microenvironment

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