Overcoming resistance to immune checkpoint inhibitors in hepatocellular carcinoma: Challenges and opportunities

Xie, Qingqing; Zhang, Pengfei; Wang, Yuanyuan; Mei, Wuxuan; Zeng, Changchun

doi:10.3389/fonc.2022.958720

Cited by 10 publications

(6 citation statements)

References 87 publications

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“…To gain deeper insight into the potential mechanisms behind the antitumor immune response induced by Ru1105 in combination with 808 nm laser in mice, we analyzed the immune cells from the vaccinated mice by flow cytometry. − The existence of cytotoxic T cells (CTLs, CD8 + T cells) within tumors serves as a distinctive indicator of specific immune responses, correlating with a favorable prognosis across various cancer types. Additionally, inducers of ICD ultimately prompt a T cell-mediated immune response, involving the activation of CD8 + T cells.…”

Section: Resultsmentioning

confidence: 99%

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Tu,

Li,

Ding

et al. 2024

J. Am. Chem. Soc.

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Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects in deepseated tumors remains challenging. Herein, we introduce a novel selfassembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λ em = 1105 nm), as a first example of a Ru(II) supramolecular ICD inducer. Ru1105 synergistically potentiates immunomodulatory responses and reduces adverse effects in deep-seated tumors through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting of tumor cells, precision organelle localization, and improved tumor penetration/ retention capabilities. Specifically, Ru1105 demonstrates excellent depth-activated ROS production (∼1 cm), strong resistance to diffusion, and anti-ROS quenching. Moreover, Ru1105 exhibits promising results in cellular uptake and ROS generation in cancer cells and multicellular tumor spheroids. Importantly, Ru1105 induces more efficient ICD in an ultralow dose (10 μM) compared to the conventional anticancer agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency as an ICD inducer, eliciting CD8 + T cell responses and depleting Foxp3 + T cells with minimal adverse effects. Our research lays the foundation for the design of secure and exceptionally potent metal-based ICD agents in immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Tu,

Li,

Ding

et al. 2024

J. Am. Chem. Soc.

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“…[22][23][24] Approximately 40% of HCC patients show constitutive activation of Wnt/β-catenin signaling induced by mutations in related genes. 25 Studies using HCC mouse models have confirmed that activation of Wnt/β-catenin signaling obstructed DCs recruitment, thereby promoting immune escape and resistance to PD-1 treatment. 26 Sequencing data from HCC patients treated with ICIs suggested that patients without Wnt/β-catenin mutations respond to ICIs treatment, thus providing empirical evidence for the correlation between ICIs resistance and Wnt/β-catenin mutations.…”

Section: Mutation Of Pathwaysmentioning

confidence: 99%

Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Han,

Sun,

et al. 2023

Semin Liver Dis

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Immune checkpoint inhibitors (ICIs) have emerged as effective therapeutics for multiple cancers. Nevertheless, as immunotherapeutic approaches are being extensively utilized, substantial hurdles have arisen for clinicians. These include countering ICIs resistance and ensuring precise efficacy assessments of these drugs, especially in the context of hepatocellular carcinoma (HCC). This review attempts to offer a holistic overview of the latest insights into the ICIs resistance mechanisms in HCC, the molecular underpinnings, and immune response. The intent is to inspire the development of efficacious combination strategies. This review also examines the unconventional response patterns, namely pseudoprogression (PsP) and hyperprogression (HPD). The prompt and rigorous evaluation of these treatment efficacies has emerged as a crucial imperative. Multiple clinical, radiological, and biomarker tests have been advanced to meticulously assess tumor response. Despite progress, precise mechanisms of action and predictive biomarkers remain elusive. This necessitates further investigation through prospective cohort studies in the impending future.

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“…Exosomes are expected to serve as key vehicles for MTB pathogen-associated molecular patterns (PAMPs), through which MTB s inhibit host immune responses, and promote immune escape and survival. The dynamic change and balancing tendency of cytokines is a manifestation of immune effect in many immune-related diseases ( 40 – 43 ). MTB conjugated to toll-like receptor 2 (TLR2) triggers mast cells to release exosomes containing high levels of chemokine (C-C motif) ligand 2 (CCL2), IL-4, and IL-13, and causes macrophage M2 polarization, which potentiates the immune escape effect of MTB ( 44 ).…”

Section: The Roles and Mechanisms Of Exosomes In Tbmentioning

confidence: 99%

Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications

Sun,

Li,

Zhao

et al. 2024

Front. Immunol.

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Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (MTB), remains one of the most prevalent and deadly infectious diseases worldwide. Currently, there are complex interactions between host cells and pathogens in TB. The onset, progression, and regression of TB are correlated not only with the virulence of MTB but also with the immunity of TB patients. Exosomes are cell-secreted membrane-bound nanovesicles with lipid bilayers that contain a variety of biomolecules, such as metabolites, lipids, proteins, and nucleic acids. Exosome-mediated cell−cell communication and interactions with the microenvironment represent crucial mechanisms through which exosomes exert their functional effects. Exosomes harbor a wide range of regulatory roles in physiological and pathological conditions, including MTB infection. Exosomes can regulate the immune response, metabolism, and cellular death to remodel the progression of MTB infection. During MTB infection, exosomes display distinctive profiles and quantities that may act as diagnostic biomarkers, suggesting that exosomes provide a revealing glimpse into the evolving landscape of MTB infections. Furthermore, exosomes derived from MTB and mesenchymal stem cells can be harnessed as vaccine platforms and drug delivery vehicles for the precise targeting and treatment of TB. In this review, we highlight the functions and mechanisms through which exosomes influence the progression of TB. Additionally, we unravel the critical significance of exosomal constituents in the diagnosis and therapeutic applications of TB, aiming to offer novel perspectives and strategies for combating TB.

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Overcoming resistance to immune checkpoint inhibitors in hepatocellular carcinoma: Challenges and opportunities

Cited by 10 publications

References 87 publications

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications

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