Page 8 - TD-3-3

Tumor Discovery Immune and epigenetic therapies for TNBC

2 Department of Chemical Pathology, University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu State, Nigeria
3 Department of Anatomy, University of Medical Science, Ondo, Ondo State, Nigeria
4 Department of Computer Engineering and Informatics, Saint Petersburg Electrotechnical University, Saint Petersburg, Saint Petersburg,
Russia
5 Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo
State, Nigeria
6 Department of Chemistry, University of Wolverhampton, Wolverhampton, West Midlands, United Kingdom
7 School of Medicine, University for Development Studies, Tamale, Northern Region of Ghana, Ghana
8 Department of Public Health, University of Illinois Springfield, Springfield, Illinois, United States of America
9 Department of Biology, University of Texas at Tyler, Tyler, Texas, United States of America
10 Department of Biology and Ecological Sciences, Universita Della Calabria, Rende, Italy

1. Introduction Medicines Agency and the United States Food and Drug
Administration have approved various treatment regimens
Triple-negative breast cancer (TNBC) is a breast cancer combining chemotherapy and immunotherapy for TNBC
(BC) subtype defined by the absence of human epidermal patients.
growth factor receptor 2 (HER2), estrogen receptor (ER),
1,2
and progesterone receptor (PR) expression. As the BC According to recent research, 13,14 neoadjuvant
with the most aggressive trait and presenting with the immunotherapy in combination with chemotherapy
worst prognosis, TNBC is distinguished from amplified increases pathological complete response rates in early-
tumors expressing HER2 and hormone receptor-positive stage TNBC. The effectiveness of immunotherapy may be
(HR ) cancers. According to Lin et al., it is characterized impacted by the role that epigenetics plays in controlling
3
+
by a poor prognosis coupled with early death rates and the infiltration and activation of immune cells into the
recurrence in Stages I–III (which is often operable), as well tumor microenvironment (TME). 15,16 Thus, focusing on
as lower overall survival (OS) in Stage IV (in an inoperable epigenetic modifications offers a potential strategy for
setting). 4,5 TNBC immunotherapy, especially when paired with
therapies such as immune checkpoint inhibitors (ICIs),
By identifying and killing cancer cells based on tumor-
specific antigens or stress-induced chemical expression, to enhance patients’ quality of life, and survival. This
the immune system’s role in cancer surveillance is critical, review aims to investigate how the regulation of immune
checkpoint molecules, tumor-associated antigens, and
thus preventing potential injury to the body. Even with immune cell infiltration through epigenetics influences the
6
this defense against carcinogenesis and preservation of anti-tumor immune response in the microenvironment of
cellular homeostasis, immune evasion causes poor tumor TNBC.
7
antigen presentation, limiting immunotherapy’s efficacy in
TNBC. Genetic and epigenetic changes, such as aberrant 2. The TNBC microenvironment and
RNA splicing, contribute to this evasion strategy. Due to immune modulation
8
TNBC’s low genetic mutation frequency, it differs from
other solid tumors. This emphasizes the significance of The TME is an intricate network of different cell types,
epigenetic modifications in the formation of aggressive extracellular matrix elements, and signaling chemicals. The
phenotypes and the progression of cancer. 9 TME plays a crucial role in controlling the immune system
and influencing the progression of TNBC, displaying both
Cancer can result from the accumulation of mutations 17
and epigenetic changes in tumor-suppressor genes and immunosuppressive and immunoreactive properties.
17
oncogenes. Growing research indicates that epigenetic According to Zheng et al., the subclassification of
10
modifications are involved in several biological functions TNBCs into “tumor-immune microenvironment (TIME)
of tumor cells, such as invasion, metastasis, proliferation, subtypes” based on TME constituents aids in the prediction
and metabolic reprogramming. 11,12 These functions are of outcomes and suggests personalized treatments based
influenced by the interactions between cancerous cells on unique TNBC characteristics.
and their surrounding environment. Treatment for Myeloid-derived suppressor cells (MDSCs), tumor-
10
TNBC mostly consists of systemic chemotherapy instead infiltrating lymphocytes (TILs), and regulatory T-cells
of targeted therapies because it lacks HER2 and HRs. (Tregs) are the biological constituents of the TNBC
Consequently, regulatory agencies such as the European microenvironment, with recent studies employ multi-

Volume 3 Issue 3 (2024) 2 doi: 10.36922/td.3383