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

Mussa A 1 , Ismail NH 1 , Hamid M 2 , Al-Hatamleh MAI 3 , Bragoli A 4 , Hajissa K 5 Show all authors , Mokhtar NF 6 , Mohamud R 7 , Uskoković V 8 , Hassan R 9

Affiliations 

  • 1 Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia
  • 2 Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Hunan Province, Changsha, 410013, China
  • 3 Division of Hematology and Oncology, Department of Medicine, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA
  • 4 Department of Immunology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
  • 5 Department of Zoology, Faculty of Science and Technology, Omdurman Islamic University, P.O. Box 382, Omdurman, Sudan
  • 6 Institute for Research in Molecular Medicine (iNFORMM), Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia
  • 7 Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia. [email protected]
  • 8 TardigradeNano LLC, Irvine, CA, 92604, USA
  • 9 Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kota Bharu , Kelantan, 16150, Malaysia. [email protected]
J Exp Clin Cancer Res, 2024 Nov 28;43(1):312.
PMID: 39609700 DOI: 10.1186/s13046-024-03218-1

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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