Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging

Kurioka, Ayako; Klenerman, Paul

doi:10.1016/j.smim.2023.101816

Cited by 11 publications

(4 citation statements)

References 387 publications

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“…The TME of liver tumor is characterized by the infiltration of tumor-infiltrating lymphocytes, including T cells, unconventional T cells, B cells, and NK. Unconventional T cells include natural killer T, (NKT), mucosal-associated T cells (MAIT), and γδT cells ( 41 , 42 ). The anti-tumor immune response is mediated by cytotoxic CD8 + T cells (CTLs), NK cells, NKT cells, γ δ T cells, and dendritic cells (DCs).…”

Section: The Interaction Between Yap1 and Immune Molecules In Liver T...mentioning

confidence: 99%

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Gao,

Gong,

et al. 2024

Front. Immunol.

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Liver cancer is the third leading of tumor death, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immune checkpoint inhibitors (ICIs) are yielding much for sufferers to hope for patients, but only some patients with advanced liver tumor respond. Recent research showed that tumor microenvironment (TME) is critical for the effectiveness of ICIs in advanced liver tumor. Meanwhile, metabolic reprogramming of liver tumor leads to immunosuppression in TME. These suggest that regulating the abnormal metabolism of liver tumor cells and firing up TME to turn “cold tumor” into “hot tumor” are potential strategies to improve the therapeutic effect of ICIs in liver tumor. Previous studies have found that YAP1 is a potential target to improve the efficacy of anti-PD-1 in HCC. Here, we review that YAP1 promotes immunosuppression of TME, mainly due to the overstimulation of cytokines in TME by YAP1. Subsequently, we studied the effects of YAP1 on metabolic reprogramming in liver tumor cells, including glycolysis, gluconeogenesis, lipid metabolism, arachidonic acid metabolism, and amino acid metabolism. Lastly, we summarized the existing drugs targeting YAP1 in the treatment of liver tumor, including some medicines from natural sources, which have the potential to improve the efficacy of ICIs in the treatment of liver tumor. This review contributed to the application of targeted YAP1 for combined therapy with ICIs in liver tumor patients.

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Section: The Interaction Between Yap1 and Immune Molecules In Liver T...mentioning

confidence: 99%

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Gao,

Gong,

et al. 2024

Front. Immunol.

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“…Accumulation of SnCs during aging is due to the decrease of immune surveillance, probably related to dysregulation of pathways involved in the immune system activation 41 , 42 . Different mechanisms have been highlighted and SnCs impact a large panel of immune components such as T-cells, macrophages, or Natural Killers (NK) 43 , 44 . Immunotherapies belong to the field of research in which the development of specific inhibitors or regulators presents the most significant advances in therapy development.…”

Section: Immunotherapies and Cell Therapies Associated With Senolytic...mentioning

confidence: 99%

Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment

Lelarge,

Capelle,

Oger

et al. 2024

npj Aging

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The involvement of cellular senescence in the initiation and propagation of diseases is clearly characterized, making the elimination of senescent cells essential to treat age-related diseases. The development of senolytic drugs demonstrated that targeting these cells limits the deterioration of patients’ condition, by inducing apoptosis. Nevertheless, the first generations of senolytics which has been developed displayed their activities through specific mechanisms and demonstrated several limitations during clinical development. However, the rational to eliminate senescent cells remains evident, with the necessity to develop specific therapies in a context of diseases and tissues. The evolutions in the field of drug discovery open the way to a new generation of senolytic therapies, such as immunological approaches (CAR-T cells, Antibody-Drug Conjugated or vaccines), which require preliminary steps of research to identify markers specifically expressed on senescent cells, demonstrating promising specific effects. Currently, the preclinical development of these strategies appears more challenging to avoid strong side effects, but the expected results are commensurate with patients’ hopes for treatments. In this review, we highlight the fact that the classical senolytic approach based on drug repurposing display limited efficacy and probably reached its limits in term of clinical development. The recent development of more complex therapies and the extension of interest in the domain of senescence in different fields of research allow to extend the possibility to discover powerful therapies. The future of age-related diseases treatment is linked to the development of new approaches based on cell therapy or immunotherapy to offer the best treatment for patients.

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“…These cells likely homed to the airways as highly activated MAIT cells and invariant NK T-cells were found in the lungs of individuals with COVID-19 where they were associated with an improved clinical outcome [ 143 ]. Peripheral MAIT cells are reduced in older adults; however, mucosal numbers still need to be assessed in older adults [ 144 ]. MAIT cells are responsive to signals from local microbiota in early life and may have longer lasting consequences for tissue repair and antiviral immunity [ 145 ].…”

Section: Disease Effects Of Respiratory Viral Infectionsmentioning

confidence: 99%

Diverging patterns in innate immunity against respiratory viruses during a lifetime: lessons from the young and the old

Smits,

Jochems

2024

Eur Respir Rev

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Respiratory viral infections frequently lead to severe respiratory disease, particularly in vulnerable populations such as young children, individuals with chronic lung conditions and older adults, resulting in hospitalisation and, in some cases, fatalities. The innate immune system plays a crucial role in monitoring for, and initiating responses to, viruses, maintaining a state of preparedness through the constant expression of antimicrobial defence molecules. Throughout the course of infection, innate immunity remains actively involved, contributing to viral clearance and damage control, with pivotal contributions from airway epithelial cells and resident and newly recruited immune cells. In instances where viral infections persist or are not effectively eliminated, innate immune components prominently contribute to the resulting pathophysiological consequences. Even though both young children and older adults are susceptible to severe respiratory disease caused by various respiratory viruses, the underlying mechanisms may differ significantly. Children face the challenge of developing and maturing their immunity, while older adults contend with issues such as immune senescence and inflammaging. This review aims to compare the innate immune responses in respiratory viral infections across both age groups, identifying common central hubs that could serve as promising targets for innovative therapeutic and preventive strategies, despite the apparent differences in underlying mechanisms.

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Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging

Cited by 11 publications

References 387 publications

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy

Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment

Diverging patterns in innate immunity against respiratory viruses during a lifetime: lessons from the young and the old

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