Targeting immunosenescence for improved tumor immunotherapy DOI Creative Commons
Zaoqu Liu, Lulu Zuo, Zhaokai Zhou

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Oct. 28, 2024

Abstract Tumor immunotherapy has significantly transformed the field of oncology over past decade. An optimal tumor would ideally elicit robust innate and adaptive immune responses within microenvironment (TIME). Unfortunately, system experiences functional decline with chronological age, a process termed “immunosenescence,” which contributes to impaired against pathogens, suboptimal vaccination outcomes, heightened vulnerability various diseases, including cancer. In this context, we will elucidate hallmarks molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, disease levels. The role tumorigenesis senescence‐related extracellular matrix (ECM) also been addressed. Recognizing that is dynamic influenced by factors, evaluate treatment strategies targeting mechanisms, as well methods for cell, organ restoration, present emerging approaches immunotherapy. overarching goal research prevent development, recurrence, metastasis, ultimately improving patient prognosis. Our review aims reveal latest advancements prospective directions research, offering theoretical basis development practical anti‐immunosenescence anti‐tumor strategies.

Language: Английский

Hallmarks of T cell aging DOI
Marı́a Mittelbrunn, Guido Kroemer

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(6), P. 687 - 698

Published: May 13, 2021

Language: Английский

Citations

384
Immune ageing at single-cell resolution DOI Open Access
Denis A. Mogilenko,

Irina Shchukina,

Maxim N. Artyomov

et al.

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(8), P. 484 - 498

Published: Nov. 23, 2021

Language: Английский

Citations

256
Age-associated remodeling of T cell immunity and metabolism DOI Creative Commons
SeongJun Han, Peter Georgiev, Alison E. Ringel

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 35(1), P. 36 - 55

Published: Dec. 5, 2022

Language: Английский

Citations

68
T cell aging and Alzheimer’s disease DOI Creative Commons
Lin Guo, Xiaoting Li, Timothy Gould

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 4, 2023

The brain has long been considered an immune-privileged organ due to the presence of blood-brain barrier (BBB). However, recent discoveries have revealed underestimated role T cells in through meningeal lymphatic system. Age is primary risk factor for Alzheimer's disease (AD), resulting marked age-dependent changes cells. Manipulating peripheral cell immune response shown impact AD, but relationship between aging and AD remains poorly understood. Given limited success targeting amyloid beta (Aβ) growing evidence cells' involvement non-lymphoid aging, a deeper understanding context crucial advancing therapeutic progress. In this review, we comprehensively examine existing studies on offer integrated perspective their interconnections aging. This can inform development new interventions prevent or treat AD.

Language: Английский

Citations

22
T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease DOI Creative Commons

Junjian Zeng,

Zhiqiang Liao,

Hanqin Yang

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 193, P. 106461 - 106461

Published: March 2, 2024

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of β-amyloid (Aβ) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding extent role adaptive immune responses AD has been quite limited. T cells, as essential members system, exhibit quantitative functional abnormalities brains patients. Dysfunction blood-brain barrier (BBB) considered one factors leading to cell infiltration. Moreover, degree neuronal loss correlated quantity cells. We first describe differentiation subset functions peripheral cells patients provide an overview key findings related BBB dysfunction how infiltrate brain parenchyma through BBB. Furthermore, we emphasize risk associated AD, including Aβ, Tau protein, microglial apolipoprotein E (ApoE), neuroinflammation. discuss their regulation activation proliferation, well connection between neurodegeneration, Understanding innate response crucial for providing comprehensive personalized therapeutic strategies AD.

Language: Английский

Citations

13
Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis DOI Creative Commons
Fatemeh Shirafkan,

Luca Hensel,

Kristin Rattay

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 20, 2024

The intricate balance of immune reactions towards invading pathogens and tolerance self is pivotal in preventing autoimmune diseases, with the thymus playing a central role establishing maintaining this equilibrium. induction involves elimination self-reactive T cells, mechanism essential for averting autoimmunity. Disruption thymic cell selection mechanisms can lead to development diseases. In dynamic microenvironment thymus, migration interactions stromal cells are critical processes that ensure self-tolerance. Thymic epithelial particularly significant context, presenting self-antigens inducing negative autoreactive cells. Further, synergistic roles fibroblasts, B dendritic antigen presentation, regulatory responses tightly regulated. This review article collates these insights, offering comprehensive examination multifaceted tissue homeostasis establishment its implications prevention Additionally, developmental pathways explored, highlighting how genetic aberrations disrupt architecture function, leading conditions. impact infections on another area, potentially triggering autoimmunity by altering homeostasis. Overall, underscores integral discussing insights into potential therapeutic strategies examining putative avenues future research developing thymic-based therapies treating

Language: Английский

Citations

13
Epigenetic quantification of immunosenescent CD8+ TEMRA cells in human blood DOI
Ahto Salumets,

Liina Tserel,

Pauliina Rumm

et al.

Aging Cell, Journal Year: 2022, Volume and Issue: 21(5)

Published: April 9, 2022

Abstract Age‐related changes in human T‐cell populations are important contributors to immunosenescence. In particular, terminally differentiated CD8 + effector memory CD45RA TEMRA cells and their subsets have characteristics of cellular senescence, accumulate older individuals, increased age‐related chronic inflammatory diseases. a detailed profiling among individuals over 65 years age, we found high interindividual variation populations. proportions correlated positively with cytomegalovirus (CMV) antibody levels, however, not the chronological age. analysis 90 inflammation proteins, identified plasma TRANCE/RANKL levels associate several populations, including its CD28 − subsets. Given strong potential as biomarker for immunosenescence, used deep‐amplicon bisulfite sequencing match frequencies flow cytometry CpG site methylation developed computational model predict cell from whole blood genomic DNA. Our findings confirm association CMV infection provide novel tool throughput epigenetic quantification

Language: Английский

Citations

35
Immune aging in multiple sclerosis is characterized by abnormal CD4 T cell activation and increased frequencies of cytotoxic CD4 T cells with advancing age DOI Creative Commons
Leah Zuroff, Ayman Rezk, Koji Shinoda

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 82, P. 104179 - 104179

Published: July 19, 2022

Immunosenescence (ISC) describes age-related changes in immune-system composition and function. Multiple sclerosis (MS) is a lifelong inflammatory condition involving effector regulatory T-cell imbalance, yet little known about ISC MS. We examined age-associated circulating T cells MS compared to normal controls (NC).

Language: Английский

Citations

32
Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging DOI Creative Commons
Ayako Kurioka, Paul Klenerman

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101816 - 101816

Published: Aug. 1, 2023

Unconventional T cells include γδ cells, invariant Natural Killer (iNKT) and Mucosal Associated Invariant (MAIT) which are distinguished from conventional by their recognition of non-peptide ligands presented non-polymorphic antigen presenting molecules rapid effector functions that pre-programmed during development. Here we review current knowledge the effect age on unconventional early life to old age, in both mice humans. We then discuss role age-associated diseases infections, highlighting similarities between members cell family context aging.

Language: Английский

Citations

18
The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience DOI Creative Commons

Marianna V. Wrona,

Rituparna Ghosh,

Kaitlyn Coll

et al.

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Oct. 16, 2024

As we age, our immune system’s ability to effectively respond pathogens declines, a phenomenon known as immunosenescence. This age-related deterioration affects both innate and adaptive immunity, compromising function leading chronic inflammation that accelerates aging. Immunosenescence is characterized by alterations in cell populations impaired functionality, resulting increased susceptibility infections, diminished vaccine efficacy, higher prevalence of diseases. Chronic low-grade further exacerbates these issues, contributing decline overall health resilience. review delves into the characteristics immunosenescence examines various intrinsic extrinsic factors aging how hallmarks fates can play crucial role this process. Additionally, it discusses impact sex, social determinants, gut microbiota on aging, illustrating complex interplay altering function. Furthermore, concept resilience explored, focusing metrics for assessing identifying strategies enhance These include lifestyle interventions such diet, regular physical activity, stress management, use gerotherapeutics other approaches. Understanding mitigating effects are developing support robust responses aged individuals.

Language: Английский

Citations

7