Co-stimulatory agonists: An insight into the immunotherapy of cancer

Pourakbari, Ramin; Hajizadeh, Farnaz; Parhizkar, Forough; Aghebati‐Maleki, Ali; Mansouri, Sanaz; Aghebati‐Maleki, Leili

doi:10.17179/excli2021-3522

Cited by 12 publications

(9 citation statements)

References 108 publications

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“…A variety of stimulatory checkpoint molecules exist on the surface of immune cells in the TME, including CD27, CD40, OX40, glucocorticoid-induced TNF receptor (GITR), and inducible co-stimulator (ICOS), which can stimulate the proliferation and activation of immune cells after activation, improve the TIME, and enhance the efficacy of anti-tumor immunotherapy ( 52 ). 4-1BB is a well-studied stimulatory receptor, which interacts with its ligand to provide a second costimulatory signal independent of CD28 signal for T-cell activation, promotes T-cell proliferation and activation, and inhibits activation-induced apoptosis (a major type of programmed cell death of T cells, referred to as AICD), thereby enhancing T-cell immune killing function; moreover, binding of 4-1BB to its ligands can induce the activation of cells, such as monocytes, DCs, etc., and the secretion of corresponding cytokines, which plays a promoting role in immune regulation ( 53 ).…”

Section: Therapeutic Strategies Based On Tme Stimulatory Signalsmentioning

confidence: 99%

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bai

Cui

2022

Front. Immunol.

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Tumor immune microenvironment is a very complex system that is influenced by a wide range of factors; in this microenvironment, various immune cells, stromal cells, and cytokines can interact with tumor cells and jointly regulate this complex ecosystem. During tumor development, the tumor microenvironment (TME) shows the upregulation of inhibitory signals and downregulation of activating signals, which result in an immunosuppressive microenvironment and lead to tumor immune escape. In recent years, a variety of precision immunotherapy strategies have been developed to remodel the TME into a positive immune microenvironment by stimulating or restoring the inherent tumor inhibition ability of the immune system so as to improve anti-tumor therapeutic efficacy. This review focuses on immunotherapy strategies targeting the TME, including those that target the microenvironment to inhibit signaling, activate signaling, and specifically involve many new targets such as physical barriers, immune cells and their surface molecular receptors, cytokines, and metabolic factors. Furthermore, it summarizes the challenges faced while conducting research on the tumor immune microenvironment and the corresponding solutions.

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Section: Therapeutic Strategies Based On Tme Stimulatory Signalsmentioning

confidence: 99%

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bai

Cui

2022

Front. Immunol.

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“…TNFRSF9 (also known as 4-1BB ) is conducive to T cell activation and augments tumor immunity. The agonist anti- 4-1BB mAbs demonstrates the capacity to enhance CD8 + T cell responses to promote tumor rejection ( Buchan et al, 2018 ; Pourakbari et al, 2021 ). TNFRSF18 (also known as GITR ) combines with the GITR ligand to favor T cell proliferation, and an anti- GITR antibody agonist (TRX518) displays potent anti-tumor activity ( Zappasodi et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

An Integrated Fibrosis Signature for Predicting Survival and Immunotherapy Efficacy of Patients With Hepatocellular Carcinoma

Liu

Han

Meng

et al. 2021

Front. Mol. Biosci.

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Introduction: Fibrosis, a primary cause of hepatocellular carcinoma (HCC), is intimately associated with inflammation, the tumor microenvironment (TME), and multiple carcinogenic pathways. Currently, due to widespread inter- and intra-tumoral heterogeneity of HCC, the efficacy of immunotherapy is limited. Seeking a stable and novel tool to predict prognosis and immunotherapy response is imperative.Methods: Using stepwise Cox regression, least absolute shrinkage and selection operator (LASSO), and random survival forest algorithms, the fibrosis-associated signature (FAIS) was developed and further validated. Subsequently, comprehensive exploration was conducted to identify distinct genomic alterations, clinical features, biological functions, and immune landscapes of HCC patients.Results: The FAIS was an independent prognostic predictor of overall survival and recurrence-free survival in HCC. In parallel, the FAIS exhibited stable and accurate performance at predicting prognosis based on the evaluation of Kaplan–Meier survival curves, receiver operator characteristic curves, decision curve analysis, and Harrell’s C-index. Further investigation elucidated that the high-risk group presented an inferior prognosis with advanced clinical traits and a high mutation frequency of TP53, whereas the low-risk group was characterized by superior CD8+ T cell infiltration, a higher TIS score, and a lower TIDE score. Additionally, patients in the low-risk group might yield more benefits from immunotherapy.Conclusion: The FAIS was an excellent scoring system that could stratify HCC patients and might serve as a promising tool to guide surveillance, improve prognosis, and facilitate clinical management.

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“… 31 However, there is more evidence that CD47 blockade triggers the adaptive antitumor immune response, and most of the antitumor effect is mediated by cross-priming antigens to CD8 + T cells by CD47-activated dendritic cells. 32 , 33 Furthermore, it should be noted that the ability of CD47 blockade to promote an immune response is dependent upon the cytosolic sensing of tumor DNA by dendritic cells (DCs). Although this does not negate the approach, the degree to which efficacy is macrophage dependent is unclear.…”

Section: Trends In Clinical Trials According To Different Mechanismsmentioning

confidence: 99%

Landscape and perspectives of macrophage -targeted cancer therapy in clinical trials

Wang

Yang

et al. 2022

Molecular Therapy - Oncolytics

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Co-stimulatory agonists: An insight into the immunotherapy of cancer

Cited by 12 publications

References 108 publications

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

An Integrated Fibrosis Signature for Predicting Survival and Immunotherapy Efficacy of Patients With Hepatocellular Carcinoma

Landscape and perspectives of macrophage -targeted cancer therapy in clinical trials

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