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1.
Immunology ; 172(4): 547-565, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38566448

RESUMO

Ferroptosis, a necrotic, iron-dependent controlled cell death mechanism, is distinguished by the development of lipid peroxides to fatal proportions. Malignant tumours, influenced by iron to promote fast development, are vulnerable to ferroptosis. Based upon mounting evidence it has been observed that ferroptosis may be immunogenic and hence may complement immunotherapies. A new approach includes iron oxide-loaded nano-vaccines (IONVs), having supremacy for the traits of the tumour microenvironment (TME) to deliver specific antigens through improving the immunostimulatory capacity by molecular disintegration and reversible covalent bonds that target the tumour cells and induce ferroptosis. Apart from IONVs, another newer approach to induce ferroptosis in tumour cells is through oncolytic virus (OVs). One such oncolytic virus is the Newcastle Disease Virus (NDV), which can only multiply in cancer cells through the p53-SLC7A11-GPX4 pathway that leads to elevated levels of lipid peroxide and intracellular reactive oxygen species leading to the induction of ferroptosis that induce ferritinophagy.


Assuntos
Ferroptose , Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Animais , Microambiente Tumoral/imunologia , Espécies Reativas de Oxigênio/metabolismo , Vacinas Anticâncer/imunologia , Vírus Oncolíticos/imunologia , Terapia Viral Oncolítica/métodos
2.
Immunology ; 173(3): 442-469, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39129256

RESUMO

Cancer immunotherapy has revolutionized the treatment landscape by harnessing the power of the immune system to combat malignancies. Two of the most promising players in this field are cluster of differentiation 24 (CD24) and sialic acid-binding Ig-like lectin 10 (Siglec-10), and both of them play pivotal roles in modulating immune responses. CD24, a cell surface glycoprotein, emerges as a convincing fundamental signal transducer for therapeutic intervention, given its significant implication in the processes related to tumour progression and immunogenic evasion. Additionally, the immunomodulatory functions of Siglec-10, a prominent member within the Siglec family of immune receptors, have recently become a crucial point of interest, particularly in the context of the tumour microenvironment. Hence, the intricate interplay of both CD24 and Siglec-10 assumes a critical role in fostering tumour growth, facilitating metastasis and also orchestrating immune evasion. Recent studies have found multiple evidences supporting the therapeutic potential of targeting CD24 in cancer treatment. Siglec-10, on the other hand, exhibits immunosuppressive properties that contribute to immune tolerance within the tumour microenvironment. Therefore, we delve into the complex mechanisms through which Siglec-10 modulates immune responses and facilitates immune escape in cancer. Siglec-10 also acts as a viable target for cancer immunotherapy and presents novel avenues for the development of therapeutic interventions. Furthermore, we examine the synergy between CD24 and Siglec-10 in shaping the immunosuppressive tumour microenvironment and discuss the implications for combination therapies. Therefore, understanding the roles of CD24 and Siglec-10 in cancer immunotherapy opens exciting possibilities for the development of novel therapeutics.


Assuntos
Antígeno CD24 , Imunoterapia , Lectinas , Neoplasias , Transdução de Sinais , Evasão Tumoral , Microambiente Tumoral , Humanos , Antígeno CD24/metabolismo , Antígeno CD24/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Animais , Lectinas/imunologia , Lectinas/metabolismo , Receptores de Superfície Celular
3.
Med Oncol ; 41(7): 175, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874788

RESUMO

The immune system plays a pivotal role in the battle against cancer, serving as a formidable guardian in the ongoing fight against malignant cells. To combat these malignant cells, immunotherapy has emerged as a prevalent approach leveraging antibodies and peptides such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 to inhibit immune checkpoints and activate T lymphocytes. The optimization of gut microbiota plays a significant role in modulating the defense system in the body. This study explores the potential of certain gut-resident bacteria to amplify the impact of immunotherapy. Contemporary antibiotic treatments, which can impair gut flora, may diminish the efficacy of immune checkpoint blockers. Conversely, probiotics or fecal microbiota transplantation can help re-establish intestinal microflora equilibrium. Additionally, the gut microbiome has been implicated in various strategies to counteract immune resistance, thereby enhancing the success of cancer immunotherapy. This paper also acknowledges cutting-edge technologies such as nanotechnology, CAR-T therapy, ACT therapy, and oncolytic viruses in modulating gut microbiota. Thus, an exhaustive review of literature was performed to uncover the elusive link that could potentiate the gut microbiome's role in augmenting the success of cancer immunotherapy.


Assuntos
Microbioma Gastrointestinal , Imunoterapia , Neoplasias , Microbioma Gastrointestinal/imunologia , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Neoplasias/imunologia , Transplante de Microbiota Fecal/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Probióticos/uso terapêutico
4.
Biochim Biophys Acta Rev Cancer ; 1879(4): 189110, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38754793

RESUMO

Oncolytic viruses (OVs) are increasingly recognized as potent tools in cancer therapy, effectively targeting and eradicating oncogenic conditions while sparing healthy cells. They enhance antitumor immunity by triggering various immune responses throughout the cancer cycle. Genetically engineered OVs swiftly destroy cancerous tissues and activate the immune system by releasing soluble antigens like danger signals and interferons. Their ability to stimulate both innate and adaptive immunity makes them particularly attractive in cancer immunotherapy. Recent advancements involve combining OVs with other immune therapies, yielding promising results. Transgenic OVs, designed to enhance immunostimulation and specifically target cancer cells, further improve immune responses. This review highlights the intrinsic mechanisms of OVs and underscores their synergistic potential with other immunotherapies. It also proposes strategies for optimizing armed OVs to bolster immunity against tumors.


Assuntos
Imunoterapia , Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Vírus Oncolíticos/imunologia , Vírus Oncolíticos/genética , Terapia Viral Oncolítica/métodos , Imunoterapia/métodos , Animais
5.
Biochim Biophys Acta Rev Cancer ; 1879(5): 189170, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39127244

RESUMO

Immunotherapy has revolutionized cancer management, with antibody-based treatments leading the charge due to their superior pharmacodynamics, including enhanced effectiveness and specificity. However, these therapies are hampered by limitations such as prolonged half-lives, poor tissue and tumor penetration, and minimal oral bioavailability. Additionally, their immunogenic nature can cause adverse effects. Consequently, the focus is shifting towards small-molecule-based immunotherapies, which potentially overcome these drawbacks. Emerging as a promising alternative, small molecules offer the benefits of therapeutic antibodies and immunomodulators, often yielding synergistic effects when combined. Recent advancements in small-molecule cancer immunotherapy are notable, featuring inhibitors, agonists, and degraders that act as immunomodulators. This article delves into the current landscape of small-molecule immunotherapy in cancer treatment, highlighting novel agents targeting key pathways such as Toll-like receptors (TLR), PD-1/PD-L1, chemokine receptors, and stimulators of interferon genes (STING). The review emphasizes newly discovered molecular entities and their modulatory roles in tumorigenesis, many of which have progressed to clinical trials, that aims to provide a comprehensive snapshot of the evolving frontier in cancer treatment, driven by small-molecule immunomodulators.


Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Animais , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia
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