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Tumor Discovery Immune and epigenetic therapies for TNBC

TAMs are associated with fast proliferation and poor TNBC in an early and advanced stage. According to Llinàs-
differentiation, their infiltration into BC often correlates Arias et al., there is growing evidence that epigenetic
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with a poor prognosis. modifications – such as altered chromatin architecture
TAMs can be triggered by common TNBC and gene regulatory elements (GREs) – are important
chemotherapeutic agents, and these activated TAMs means of immune evasion. These modifications are
encourage the healing of damaged tumor tissues, leading particularly interesting because they are reversible through
to tumor resistance to chemotherapy. In addition, TAMs the inhibition of epigenetic regulators. The low frequency
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produce significant amounts of IL-10, which inhibits the of genetic mutations observed in TNBC, in contrast to
production of IL-12 by dendritic cells, thereby limiting many other solid tumors, emphasizes the significance of
immune-mediated tumor killing by CD8 T-cells. epigenetic modifications in the development of aggressive
+
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According to the previous studies, the phenotype of TAMs phenotypes and cancer progression.
is a better indicator of the effectiveness of anthracycline DNA methylation and histone modifications are
chemotherapeutics in treating TNBC than their absolute two important types of epigenetic alterations that are
quantity. 67 well-established. For instance, Table 3 examines various
An important approach to preventing TAM recruitment epigenetic mechanisms involved in TNBC. These
is to block the action of chemokines by targeting the included DNA methylation of genes such as breast
CCL2–CCR2 axis, thereby reducing the mobilization of cancer gene 1 (BRCA1) and Ras association domain
mononuclear cells from the bone marrow and lowering family member 1A (RASSF1A), histone modifications
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macrophage infiltration in the breast. Although apoptosis involving overexpression of enhancer of zeste 2 polycomb
inducers by bisphosphonate-based macrophage have been repressive complex 2 subunit and histone deacetylase 1 or
broadly utilized to deplete TAMs, the immune status 2 (HDAC1/2), non-coding RNAs like the miR-200 family
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changes from anti-tumor to immunosuppressive when and miR-221/222, and chromatin remodeling factors
TAMs undergo a phenotypic transition within the TME. including the SWI/SNF complex (AT-rich interactive
This dynamic modification highlights the critical function domain-containing protein 1A) and chromodomain
of TAMs in controlling tumor behavior and offers insights helicase DNA binding protein 1.
for assessing therapeutic efficacy. DNA methylation primarily occurs at the fifth position
Since TAMs play a part in the growth of tumors, TAM- of cytosines that precede guanosines (5mC). On the other
targeting therapeutic approaches have been developed. hand, the catalog of histone modifications is considerably
Yang et al. reported the advantages of TAM-targeting more complex, involving a variety of chemical groups and
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therapy, which includes more precise drug delivery through locations. These chemical modifications, which are finely
nanomedicines – such as nanospheres, nanocapsules, tuned, are regulated by a group of enzymes that have gained
nanomicelles, and nanoliposomes – modified biologically increasing importance in cancer research: “writers” impose
or physiochemically, and fewer harmful effects on healthy chemical traces, “erasers” remove them, and “readers”
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tissues, such as myelosuppression, gastrointestinal distress, identify the epigenetic code, enlisting additional proteins.
organ toxicity, and other typical side effects of chemotherapy Repressive histone marks or promoter hypermethylation
drugs. Recent TAMs-targeting therapeutic research has are usually associated with the silencing of neighboring
focused on the following areas: inhibition of TAM survival, genes, including tumor suppressor genes like BRCA1.
repolarization of the M2-like phenotype into the M1-like However, GREs, such as enhancers and insulators, which
phenotype, and suppression of macrophage recruitment. control the activation of gene expression programs linked
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Niu et al. also explored a strategy to eliminate TAMs in to cancer, can also be affected by epigenetic modifications,
TNBC by utilizing nanoparticles targeted at the CD206 in addition to gene promoters. Global hypomethylation of
receptor, which delivered doxorubicin effectively in a DNA has the potential to cause oncogene reactivation and
pH-sensitive manner to enhance therapeutic outcomes. genomic instability. 87
However, because TNBC is highly heterogeneous, targeted Furthermore, immunogenic antigens production
therapies concentrating on a specific TAM-related pathway stimulation and reactivation of transposable elements
frequently face obstacles that result in failure. through the use of small molecule inhibitors to chemically

3. Epigenetic modifications and effect of eliminate aberrant epigenetic markers may strengthen
the immunological response in TNBC. The immune
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alteration on immune recognition in TNBC response may be impaired, allowing tumor cells to avoid
Although limited to a small patient population, there immune surveillance due to the downregulation of antigen
has been encouraging effectiveness using ICIs in treating processing and presentation and loss of MHC Class I

Volume 3 Issue 3 (2024) 6 doi: 10.36922/td.3383