Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2025,
Volume and Issue:
44(1)
Published: April 25, 2025
Abstract
This
review
discusses
reprogramming
the
breast
tumor
immune
microenvironment
from
an
immunosuppressive
cold
state
to
immunologically
active
hot
state.
A
complex
interplay
is
revealed,
in
which
accumulation
of
metabolic
byproducts—such
as
lactate,
reactive
oxygen
species
(ROS),
and
ammonia—is
shown
impair
T-cell
function
promote
escape.
It
demonstrated
that
(TME)
dominated
by
cytokines,
including
interleukin-10
(IL-10),
transforming
growth
factorβ
(TGFβ),
IL-35.
Notably,
IL-35
produced
regulatory
T
cells
cancer
cells.
The
conversion
conventional
into
IL-35-producing
induced
cells,
along
with
inhibition
pro-inflammatory
cytokine
secretion,
contributes
suppression
anti-tumor
immunity.
further
key
checkpoint
molecules—such
PD-1,
PDL1,
CTLA-4,
TIM-3,
LAG-3,
TIGIT—are
upregulated
within
TME,
leading
Tcell
exhaustion
diminished
responses.
blockade
these
checkpoints
restore
functionality
proposed
a
strategy
convert
tumors
ones
robust
effector
cell
infiltration.
therapeutic
potential
chimeric
antigen
receptor
(CAR)T
therapy
also
explored,
targeting
specific
tumor-associated
antigens,
such
glycoproteins
tyrosine
kinases,
highlighted.
suggested
CART
efficacy
can
be
enhanced
combining
inhibitors
other
immunomodulatory
agents,
thereby
overcoming
barriers
imposed
TME.
Moreover,
role
microbiome
regulating
estrogen
metabolism
systemic
inflammation
reviewed.
Alterations
gut
microbiota
are
affect
microbiome-based
interventions
additional
means
facilitate
cold-to-hot
transition.
concluded
immunological
pathways
underpin
suppression—through
combination
strategies
involving
blockade,
therapies,
modulation—the
TME
achieved.
anticipated
enhance
infiltration
function,
improving
overall
immunotherapies
better
clinical
outcomes
for
patients.
Language: Английский
Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis
Frontiers in Oncology,
Journal Year:
2025,
Volume and Issue:
15
Published: April 25, 2025
Transforming
growth
factor-beta
(TGF-β)
has
long
been
known
to
be
associated
with
early
embryonic
development
and
organogenesis,
immune
supervision,
tissue
repair
homeostasis
in
adults.
TGF-β
complex
roles
fibrosis
cancer
that
may
opposing
at
different
stages
of
these
diseases.
Under
pathological
conditions,
overexpression
causes
epithelial–mesenchymal
transition,
deposition
extracellular
matrix,
formation
cancer-associated
fibroblasts,
leading
fibrotic
disease
or
cancer.
Fibroblasts,
epithelial
cells,
cells
are
the
most
common
targets
TGF-β,
while
TGF-β-associated
Given
critical
role
its
downstream
molecules
progression
cancer,
therapies
targeting
signaling
appear
a
promising
strategy.
Preclinical
clinical
studies
have
investigated
including
antisense
oligonucleotides,
monoclonal
antibodies,
ligand
traps.
However,
targeted
therapy
hindered
by
systemic
cytotoxicity.
This
review
discusses
molecular
mechanisms
highlights
for
as
therapeutic
strategy
related
Language: Английский