Can senolysis be used to overcome tumor immune evasion? DOI Open Access

Wally Veklych,

Thomas E. Ichim,

Robert Reznik

et al.

Journal of Stem Cell Research & Therapeutics, Journal Year: 2024, Volume and Issue: 9(1), P. 26 - 32

Published: Jan. 1, 2024

Tumor escape from immunologically mediated destruction is a well-studied phenomena and has been shown to utilize several pathways in common with physiological conditions such as pregnancy, well ocular or testicular immune privilege. Recent interest senescence revealed that senescent cells surrounding tumors contribute development of specific microenvironment may allow for escape. Senescent have reported possess “senescence associated secretory phenotype” (SASP) which produces inflammatory agents directly indirectly suppression T cell NK function. Exosomes secreted by can suppress activation, downregulate activity dendritic cells, are needed initiation immunity. Studies demonstrated reduction load increases tumor sensitivity variety therapies. We will overview supportive evidence use senolytics potentiate the efficacy immunotherapy cancer, discuss our preliminary findings regarding SenoVax™ (IND #30745), an autologous, polyvalent senolytic vaccine being developed treatment advanced non-small lung cancer.

Language: Английский

Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype DOI Creative Commons

J. P. W. Joung,

Y.‐A. Heo,

Yeonju Kim

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 17, 2025

Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although enlargement is a prominent morphological feature of cellular senescence, its functional implications unknown; moreover, how senescent cells maintain their state less understood. Here we show that an extensive remodeling actin cytoskeleton necessary for establishing senescence-associated pro-inflammatory secretory phenotype (SASP). This attributed to balancing act between the SASP regulator GATA4 mechanosensor YAP on expression Rho family GTPase RHOU. Genetic or pharmacological interventions reduce attenuate minimal effect senescence growth arrest. Mechanistically, couples nuclear localization NF-κB via Linker Nucleoskeleton Cytoskeleton (LINC) complex. RhoU protein accumulates mouse adipose tissue under senescence-inducing conditions. Furthermore, RHOU correlates during human Thus, our study highlights unexpected instructive role modulating reveals mechanical branch regulatory network. Senescent accumulate aging exhibit enlargement, function which has been unclear decades. Here, authors identify antagonistic genetic circuit hypertrophy reveal SASP.

Language: Английский

Citations

1
Characterization of senescence and nuclear reorganization in aging gingival cells DOI Creative Commons
Christian Fernández,

Diego Ormeno,

Verónica Villalobos

et al.

npj Aging, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 21, 2025

Language: Английский

Citations

0
Clinical features, diagnosis, management, and prognosis of circumscribed choroidal hemangioma DOI Creative Commons
Zuyi Yang,

D Tian,

Zeping Xie

et al.

Survey of Ophthalmology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Targeting the NLRP3 in macrophages contributes to senescence cell clearance in radiation-induced skin injury DOI Creative Commons
Gaoyu Liu, Yan Chen, Shijie Dai

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 18, 2025

The persistent accumulation of senescence cells is one the characteristics radiation-induced skin injury (RISI), leading to fibrosis and impaired healing. However, reasons why these are resistant clearance remain unclear. mouse RISI model was established using an X-ray generator, a shield used cover all areas except right leg or back for protecting surrounding tissue. ScRNA sequencing, immunohistochemistry, immunofluorescence, qPCR, western blot, primary cell co-culture system fluorescence microsphere phagocytosis assay were performed functional mechanistic investigations. dynamic changes levels multiple immune during evaluated, we found that macrophages could remove from dermis, ability gradually strengthens over time. sequencing revealed with high capacity exhibited increased NOD-like receptor family pyrin domain-containing 3 (NLRP3) expression compared those low capacity. Inhibition conditional knockout Nlrp3 in led dysfunction Further studies interleukin-33 secreted by inhibited NLRP3 their phagocytize cells, especially early stages after radiation. In addition, Nocardia rubra wall skeleton (Nr-CWS), approved immunomodulator, activate macrophage expression, reduce burden, accelerate healing RISI. This study underscored as critical intervention target immunosurveillance emphasized Nr-CWS potential therapeutic agent accelerating

Language: Английский

Citations

0
A new marker for predicting sentinel lymph node metastasis in early (cT1-2N0) breast cancer: Tumor-infiltrating lymphocytes (TILs) DOI Creative Commons
Xiaofei Ni, Weitao Wang, Huimin Sun

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0320487 - e0320487

Published: March 19, 2025

Tumor-infiltrating lymphocytes (TILs) are associated with lymph node metastasis and prognosis in breast cancer. Therefore, we explored the value of TILs predicting sentinel (SLNM) patients early-stage (cT1-2N0) cancer provided a new method for preoperative assessment SLNM status. This study included 337 who underwent surgery at our hospital from January 2022 to December 2023. The expression estrogen receptor (ER), progesterone (PR), human epidermal growth factor 2 (HER2), Ki-67 was assessed using immunohistochemistry (IHC). core needle biopsy samples were evaluated histopathologically, divided into high low groups based on density TILs. Statistical analysis conducted, predictive model established. found that had significantly lower rate compared those (P < 0.001). cT stage level identified as independent factors SLNM. ROC curve indicated has good efficacy Based results multivariate regression analysis, nomogram constructed. Our showed cancer, effect is significant Luminal triple-negative cancers.

Language: Английский

Citations

0
Bispecific antibodies combined with chemotherapy in solid tumor treatment, the path forward? DOI Creative Commons
Yici Yan, Jing Yuan,

Yanyang Peng

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Bispecific antibodies (bsAbs) introduced a novel strategy in anticancer therapy when chemotherapy alone could not meet life expectancy. Nonetheless, the efficacy of monotherapy was limited, and safety profile bsAbs combined with remained uncertain. Literature retrieval carried out through PubMed, Embase, Cochrane from inception to January, 2025. Progression-free survival (PFS), overall (OS), response rate (ORR), along adverse effects (AEs), were utilized assess safety. Publication bias calculated using Funnel plots Egger's test. Heterogeneity examined subgroup sensitivity analyses. The protocol preregistered International Prospective Register Systematic Reviews (CRD42025633628). A total 8 eligible clinical studies 2,495 patients included. Compared alone, bsAb+chemotherapy exhibited positive outcomes PFS (hazard ratio (HR): 0.52; 95% confidence interval (CI): 0.44-0.60; p<0.01), OS (HR: 0.67, CI: 0.57-0.77; ORR 0.31, 0.16-0.47; p<0.01). Subgroup analysis revealed that female patients, Asian those under 65 years age, treated IgG-like bsAb more likely benefit advantages bsAb+chemotherapy. Despite occurrence leukopenia, metabolism-related, skin-related AEs, RR AEs other systems showed no statistical significance. BsAb+chemotherapy superior especially receiving bsAb. Additionally, while associated are generally manageable, there is still room for improvement. https://www.crd.york.ac.uk/prospero/, identifier CRD42025633628.

Language: Английский

Citations

0
SOX2 drives fetal reprogramming and reversible dormancy in colorectal cancer DOI Creative Commons
Anna Baulies, Verónica Moncho-Amor, Diana Drago-García

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Abstract Cellular plasticity plays critical roles in tissue regeneration, tumour progression and therapeutic resistance. However, the mechanism underlying this cell state transition remains elusive. Here, we show that transcription factor SOX2 induces fetal reprogramming reversible dormancy colorectal cancer (CRC). expression correlates with poor prognosis human primary metastatic adenocarcinomas. In mouse CRC models, rare slow-cycling + SCA1 cells are detected early Apc -deleted tumours undergo slow clonal expansion over time. contrast, clones were found proliferative advanced -/- ;Kras G12D/+ ;p53 ;Tgfbr2 (AKPT) tumours, accompanied by dynamic from LGR5 to - cells. Using transgenic demonstrate ectopic of inhibits intestinal lineage differentiation reprogramming. SOX2+ adopt cycle states depending on its level. High results hyperproliferation, whereas low levels induce senescence-mediated dormancy. We find loss p53 can reverse SOX2-induced senescence, line dormant exit observed tumours. Finally, is induced 5-FU treatment CRC. SOX2-expressing organoids exhibit increased tolerance chemotherapy treatment, whilst deletion AKPT sensitises drug responses. propose promotes

Language: Английский

Citations

2
Can senolysis be used to overcome tumor immune evasion? DOI Open Access

Wally Veklych,

Thomas E. Ichim,

Robert Reznik

et al.

Journal of Stem Cell Research & Therapeutics, Journal Year: 2024, Volume and Issue: 9(1), P. 26 - 32

Published: Jan. 1, 2024

Tumor escape from immunologically mediated destruction is a well-studied phenomena and has been shown to utilize several pathways in common with physiological conditions such as pregnancy, well ocular or testicular immune privilege. Recent interest senescence revealed that senescent cells surrounding tumors contribute development of specific microenvironment may allow for escape. Senescent have reported possess “senescence associated secretory phenotype” (SASP) which produces inflammatory agents directly indirectly suppression T cell NK function. Exosomes secreted by can suppress activation, downregulate activity dendritic cells, are needed initiation immunity. Studies demonstrated reduction load increases tumor sensitivity variety therapies. We will overview supportive evidence use senolytics potentiate the efficacy immunotherapy cancer, discuss our preliminary findings regarding SenoVax™ (IND #30745), an autologous, polyvalent senolytic vaccine being developed treatment advanced non-small lung cancer.

Language: Английский

Citations

0