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Cells. 2019 Dec 20;9(1). pii: E33. doi: 10.3390/cells9010033.

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor-An Opportunity for Cancer Treatment.

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Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kelantan, Malaysia.
Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan 16150, Malaysia.
Translational Immunology and Nanotechnology Unit, School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia.
Université de Lorraine, CNRS, LCPM, F-5400 Nancy, France.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences. University of Macau, Macao 999078, China.
Cancer Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, 34110 Doha, Qatar.
Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kelantan 16150, Malaysia.


Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy.


TNF; immunosuppressive; immunotherapy; nanoparticles; regulatory T cells

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