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Tumor Discovery

REVIEW ARTICLE
Immune modulation and epigenetic therapies

for enhanced outcome of treatment in triple-
negative breast cancer

Vitalis Chukwuemeka Okwor 1 , Chika Juliet Okwor 2 ,
Stephen Abiodun Musayayi 3 , Tolulope Judah Gbayisomore * ,
3
Innocent Joseph 4 , Isaac Olamide Babalola 5 , Lucky Aighowmanfe Ayeni 6 ,
Abdul-Hanan Saani Inusah 7 , Rufus Oluwagbemileke Ajayi 8 ,
Feranmi Emmanuel Obe 9 , and Bertha Michael Akpan 10

1 Department of Radiation Medicine, University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu
State, Nigeria

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by
the absence of human epidermal growth factor receptor 2, estrogen receptor, and
progesterone receptor expression. While traditional TNBC treatment primarily relies
on systemic chemotherapy, epigenetic modification has an important role in immune
evasion and tumor progression. Recent classifications of TNBC into “hot” and “cold”
tumors, based on immune activity and mutation burden, have revealed that poor
response to immune checkpoint inhibitors (ICIs) in these tumors is due to low tumor-
infiltrating lymphocytes and the presence of immunosuppressive cells. Emerging
*Corresponding author: treatments such as ICIs and poly(ADP-ribose) polymerase inhibitors offer promising
Tolulope Judah Gbayisomore alternatives. The tumor microenvironment (TME) shapes immune responses in
(tolulopegbayisomore@gmail.com) TNBC, and a limited subset of patients has shown encouraging responses to ICIs in
Citation: Okwor VC, Okwor CJ, treating TNBC at both early and advanced stages. However, combination therapies
Musayayi SA, et al. Immune face challenges, including medication interactions and side effects. Epigenetic
modulation and epigenetic therapies
for enhanced outcome of treatment modulators, such as histone deacetylase and DNA methyltransferase inhibitors, also
in triple-negative breast cancer. show promise in reversing epigenetic changes by enhancing anti-tumor immunity
Tumor Discov. 2024;3(3):3383. in TNBC. The frequent expression of indoleamine 2,3-dioxygenase 1 (IDO1) in TNBC,
doi: 10.36922/td.3383 which catalyzes the conversion of tryptophan to kynurenine, contributes to immune
Received: April 8, 2024 suppression in TNBC patients. High IDO1 levels impair the tumoricidal activity of
Accepted: July 16, 2024 natural killer cells and correlate with poor responses to anti-PD-L1 therapy, which
can be improved using IDO1 inhibitors. Targeting myeloid-derived suppressor cells,
Published Online: October 4, 2024 regulatory T-cells, and tumor-associated macrophage, along with utilizing epigenetic
Copyright: © 2024 Author(s). mechanisms, show promise in modulating the immunosuppressive TME in TNBC.
This is an Open-Access article Combining these approaches with standard therapies, along with biomarker-guided
distributed under the terms of the
Creative Commons Attribution patient selection, can enhance treatment efficacy. Clinical trials and preclinical models
License, permitting distribution, are essential for optimizing these strategies. This study emphasizes the importance
and reproduction in any medium, of understanding the mechanisms of modulation, tumor-immune interactions, and
provided the original work is
properly cited. the potential of epigenetic therapies in improving treatment outcomes in TNBC.
Publisher’s Note: AccScience
Publishing remains neutral with Keywords: Triple-negative breast cancer; Epigenetic modifications; Immune modulation;
regard to jurisdictional claims in
published maps and institutional Combination therapies
affiliations.

Volume 3 Issue 3 (2024) 1 doi: 10.36922/td.3383