Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer

Ali Mussa; Nor Hayati Ismail; Mahasin Hamid; Mohammad A I Al-Hatamleh; Anthony Bragoli; Khalid Hajissa; Noor Fatmawati Mokhtar; Rohimah Mohamud; Vuk Uskoković; Rosline Hassan

doi:10.1186/s13046-024-03218-1

Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer

J Exp Clin Cancer Res. 2024 Nov 28;43(1):312. doi: 10.1186/s13046-024-03218-1.

Authors

Ali Mussa^{1

2}, Nor Hayati Ismail¹, Mahasin Hamid^{3

4}, Mohammad A I Al-Hatamleh⁵, Anthony Bragoli⁶, Khalid Hajissa⁷, Noor Fatmawati Mokhtar⁸, Rohimah Mohamud⁹, Vuk Uskoković^{10

11}, Rosline Hassan¹²

Affiliations

¹ Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia.
² Department of Biology, Faculty of Education, Omdurman Islamic University, P.O. Box 382, Omdurman, Sudan.
³ Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Hunan Province, Changsha, 410013, China.
⁴ Department of Zoology, Faculty of Sciences and Information Technology, University of Nyala, Nyala, 63311, Sudan.
⁵ Division of Hematology and Oncology, Department of Medicine, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁶ Department of Immunology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
⁷ Department of Zoology, Faculty of Science and Technology, Omdurman Islamic University, P.O. Box 382, Omdurman, Sudan.
⁸ Institute for Research in Molecular Medicine (iNFORMM), Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia.
⁹ Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia. [email protected].
¹⁰ TardigradeNano LLC, Irvine, CA, 92604, USA.
¹¹ Division of Natural Sciences, Fullerton College, Fullerton, CA, 92832, USA.
¹² Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia. [email protected].

Abstract

Breast cancer (BC) is the most frequently diagnosed malignancy among women. It is characterized by a high level of heterogeneity that emerges from the interaction of several cellular and soluble components in the tumor microenvironment (TME), such as cytokines, tumor cells and tumor-associated immune cells. Tumor necrosis factor (TNF) receptor 2 (TNFR2) appears to play a significant role in microenvironmental regulation, tumor progression, immune evasion, drug resistance, and metastasis of many types of cancer, including BC. However, the significance of TNFR2 in BC biology is not fully understood. This review provides an overview of TNFR2 biology, detailing its activation and its interactions with important signaling pathways in the TME (e.g., NF-κB, MAPK, and PI3K/Akt pathways). We discuss potential therapeutic strategies targeting TNFR2, with the aim of enhancing the antitumor immune response to BC. This review provides insights into role of TNFR2 as a major immune checkpoint for the future treatment of patients with BC.

Keywords: CD120b; Immune checkpoint; Immunosuppressive TME; TNF; TNFRSF1B.

Publication types

Review

MeSH terms

Breast Neoplasms* / immunology
Breast Neoplasms* / metabolism
Breast Neoplasms* / pathology
Female
Humans
Receptors, Tumor Necrosis Factor, Type II* / metabolism
Signal Transduction*
Tumor Microenvironment*

Substances

Receptors, Tumor Necrosis Factor, Type II