Biomaterials, Journal Year: 2023, Volume and Issue: 301, P. 122233 - 122233
Published: June 28, 2023
Language: Английский
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Aug. 9, 2024
Resistance to radiotherapy is a major barrier during cancer treatment. Here using genome-scale CRISPR/Cas9 screening, we identify CD274 gene, which encodes PD-L1, confer lung cell resistance ionizing radiation (IR). Depletion of endogenous PD-L1 delays the repair IR-induced DNA double-strand breaks (DSBs) and loss downregulates non-homologous end joining (NHEJ) while overexpression upregulates NHEJ. IR induces translocation from membrane into nucleus dependent on deglycosylation at N219 CMTM6 leads recruitment DSBs foci. interacts with Ku in enhances binding DSB DNA. The interaction between IgC domain core required for accelerate NHEJ-mediated produce radioresistance. Thus, addition its immune inhibitory activity, acts as mechanistic driver cancer. authors find that radiation-induced double-strand-breaks facilitate nucleus, leading promotion
Language: Английский
Citations
6
Journal of Zhejiang University (Medical Sciences), Journal Year: 2024, Volume and Issue: 53(1), P. 1 - 14
Published: Jan. 5, 2024
Tumor cells adapt their metabolism to meet the demands for energy and biosynthesis. Mitochondria, pivotal organelles in metabolic reprogramming of tumor cells, contribute tumorigenesis cancer progression significantly through various dysfunctions both immune cells. Alterations mitochondrial dynamics signaling pathways exert crucial regulatory influence on activation, proliferation, differentiation The microenvironment orchestrates activation functionality tumor-infiltrating by inducing shifts dynamics, thereby facilitating establishment a immunosuppressive microenvironment. Stress-induced leakage DNA contributes multifaceted effects anti-tumor responses activating multiple natural signals, including cGAS-STING, TLR9, NLRP3. Moreover, DNA-mediated immunogenic cell death emerges as promising avenue immunotherapy. Additionally, reactive oxygen species, factor tumorigenesis, drives formation changing composition within This review focuses intrinsic relationship between biology from angles. We explore core role mitochondria dynamic interplay host facilitate development targeted strategies
Language: Английский
Citations
5
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: July 8, 2024
Exosome-derived microRNAs (miRNAs) are biomacromolecules and nanoscale extracellular vesicles originating from intracellular compartments that secreted by most cells into the space. This review examines formation function of exosomal miRNAs in biological information transfer, explores pathogenesis vitiligo, highlights relationship between vitiligo. The aim is to deepen understanding how influence immune imbalance, oxidative stress damage, melanocyte-keratinocyte interactions, melanogenesis disorders development enhanced may contribute potential diagnostic therapeutic options for
Language: Английский
Citations
5
Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(5), P. 1789 - 1827
Published: Aug. 28, 2022
Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged a promising platform for regulating immune responses. Owing their outstanding advantages such high biocompatibility, prominent structural stability, and loading capacity, cellular suitable delivering various immunomodulatory molecules, small nucleic acids, peptides, proteins. Immunomodulation induced by has been exploited modulate cell behaviors, is considered novel cell-free immunotherapeutic strategy the prevention treatment of diverse diseases. Here we review emerging concepts new advances in leveraging activate or suppress responses, with aim explicate applications immunomodulation. We overview general considerations principles design engineered tailored activities. also discuss engineering immunotherapies treating major
Language: Английский
Citations
21
The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(8)
Published: April 15, 2025
ABSTRACT Colorectal cancer (CRC) shows a limited response to programmed death‐ligand 1 (PD‐L1) immunotherapies. Akkermansia muciniphila (AKK) may enhance tumor immunity. This study examines how its Outer Membrane Vesicles (OMVs) and Amuc_1434 influence PD‐L1 expression CD8+ T cell activity in CRC. OMVs were isolated their characteristics examined through transmission electron microscopy Western blotting. was quantified via blot, while proliferation measured using flow cytometry. Cytokine production (interferon‐gamma (IFN‐γ) interleukin‐2 (IL‐2)) evaluated ELISA. A CRC mouse model employed examine impact on growth immune infiltration. In cells, treatment with AKK‐derived (AKK‐OMVs) significantly downregulated ( p < 0.05) markedly increased the levels of IFN‐γ IL‐2 0.01). identified as key protein mediating these effects. vivo, AKK‐OMVs substantially reduced volume 0.01) enhanced infiltration into microenvironment Additionally, AKK‐OMVs‐treated mice showed activation markers within tissue, further indicating antitumor reveals that AKK‐OMVs, particularly those containing Amuc_1434, can modulate potentiate cell‐mediated immunity These findings suggest novel approach overcoming resistance checkpoint inhibitors
Language: Английский
Citations
0
Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3912 - 3912
Published: Aug. 1, 2023
P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of small noncoding (ncRNAs) that bind components the PIWI protein family. piRNAs specifically expressed in different human tissues and regulate important signaling pathways. Aberrant expressions proteins have been associated with tumorigenesis cancer progression. Recent studies reported contained extracellular vesicles (EVs), nanosized lipid particles, key roles cell–cell communication. EVs contain several bioactive molecules, such as proteins, lipids, nucleic acids, including emerging ncRNAs. one liquid biopsy (LB) non-invasive method for detecting specific molecular biomarkers samples. LB could become crucial tool diagnosis precision oncology approach. This review summarizes current findings on types, focusing potential theranostic applications (EV-piRNAs). Their diagnostic prognostic therapeutic options also discussed.
Language: Английский
Citations
10
Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)
Published: Jan. 14, 2025
Small extracellular vesicles (sEVs), carrying PD-L1, have been implicated in immune evasion and tumor progression. However, understanding how PD-L1 sEVs are secreted still needs to be improved. We found that the secretion dynamics of is similar other sEVs. Intracellular calcium associated downstream PKC signaling plays pivotal roles releasing non-small cell lung cancer cells (NSCLC). Particularly, we observed knocking down PKCα has profound impacts on secretion, especially resting state activated state, when induced by an intracellular rise. Furthermore, our study revealed regulates expression influencing STAT1 phosphorylation nuclear translocation a p53-dependent manner. Notably, p53 can regulate localization, but it does not affect expression. This suggests significant role regulating Our findings suggest targeting modulate NSCLC may promising therapeutic strategy enhance efficacy immunotherapeutic interventions.
Language: Английский
Citations
0
Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)
Published: March 7, 2025
Limited treatment response and inadequate monitoring methods stand firmly before successful immunotherapy. Recruiting activating immune cells in the hypoxic tumor microenvironment is key to reversing suppression improving immunotherapy efficacy. In this study, biomimetic oxygen-delivering nanoparticles (CmPF) are engineered for homologous targeting hypoxia alleviation within environment. CmPF targets delivers oxygen reduce hypoxia, thereby promoting cell activity at site. addition, granzyme B-targeted positron emission tomography (PET) imaging employed monitor changes efficacy vivo. The combination of with carboplatin PD-1 inhibitors significantly suppresses growth by 2.4-fold, exhibiting potential enhance Immunohistochemistry further confirms increased expression markers, highlighting reprogramming microenvironment. This study demonstrates that enhances introduces a non-invasive PET method dynamic, real-time assessment therapeutic response.
Language: Английский
Citations
0
Biomedicines, Journal Year: 2022, Volume and Issue: 10(5), P. 1181 - 1181
Published: May 20, 2022
While promising, PD-L1 expression on tumor tissues as assessed by immunohistochemistry has been shown to be an imperfect biomarker that only applies a limited number of cancers, whereas many patients with PD-L1-negative tumors still respond anti-PD-(L)1 immunotherapy. Recent studies using patient blood samples assess immunotherapeutic responsiveness suggests promising approach the identification novel and/or improved biomarkers for In this review, we discuss advances in our evolving understanding regulation and function expression, which is foundation developing blood-based We further current knowledge clinical study results immune cells, exosomes, soluble forms peripheral blood. Finally, key challenges successful development potential use
Language: Английский
Citations
16
Advances in Orthopedics, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 7
Published: Feb. 23, 2024
Introduction.
Immunotherapy
has
been
widely
used
in
the
treatment
of
various
malignancies
with
satisfactory
results.
One
agents
for
immunotherapy
is
an
inhibitor
programmed
cell
death-1
and
its
ligands
(PD-1
PD-L1).
However,
attempts
at
utilizing
PD-1/PD-L1
osteosarcoma
have
not
yielded
favorable
This
may
be
due
to
differences
PD-L1
regulation
immune
landscape
osteosarcoma,
as
mechanism
still
poorly
understood.
Therefore,
elucidating
paramount
order
improve
results
using
immunotherapy.
Methods.
a
cross-sectional
study
conducted
Department
Anatomical
Pathology
Saiful
Anwar
Hospital
33
paraffin
blocks
confirmed
cases
osteosarcoma.
Immunohistochemical
staining
PD-L1,
STAT3,
IL6,
EGFR
was
performed.
Statistical
analyses
were
subsequently
performed
on
immunoexpression
data
these
antibodies.
Results.
expressions
found
6
(18.2%),
28
(84.8%),
30
(90.9%)
cases,
respectively.
There
significant
correlations
between
STAT3
(r
=
0.620,
Language: Английский
Citations
3