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

Abstract

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.Cells 2020, 9, 33 2 of 16 and tumor cells [6][7][8]. In contrast, TNFR2 expression was only reported on tumor cells and suppressive immune cells, suggesting that TNFR2 directly promotes cancer development [9]. Furthermore, the latest preclinical and clinical studies confirmed the implication of TNF-TNFR2 signaling in cancer proliferation and the suppression of immune response [10,11]. Consequently, blockade of TNF-TNFR2 axis could be a promising option for cancer treatment (Figure 1).On the other hand, nanotechnology provided several platforms in the field of immunotherapy and made significant advances towards safe and efficient targeting systems with positive clinical outcomes and minimal side effects; this is the so-called field of nanomedicine [12]. Despite the emerging trends of using nanoparticles in immunotherapy, no studies have investigated any type of nanocarriers to target TNFR2 on cancer cells. However, based on some previous novel reports about the effects of nanoparticles on immune homeostasis [13], especially using nanoparticles to promote TNFR2 + Foxp3 + regulatory T cells (Tregs) in inflammatory models [14,15], we have suggested in our recent perspective review the possibility of blocking TNF-TNFR2 axis via nanoparticles [16].

Antioxidant-Based Medicinal Properties of Stingless Bee Products: Recent Progress and Future Directions

“…The expression of these enzymes is stimulated in the inflammatory conditions, and therefore, inhibition of these enzymes will stop ROS production that leads to reduce oxidative stress and then an anti-inflammatory effect [ 68 , 69 ]. Since mediators of inflammation play crucial roles in various diseases (e.g., cancer and obesity) [ 70 , 71 ], SBH could also rely on these mechanisms of action in modulating the inflammatory-associated diseases.…”

“…Furthermore, nanoparticles show a promising role in controlling immune homeostasis during several inflammatory conditions [ 70 , 74 , 148 ]. Compared to the chemical synthesis for nanoparticles, the green synthesis (i.e., using natural products) provides advancement due to it is safer for the therapeutic intervention purposes and environment-friendly [ 149 , 150 ].…”

Recent Advances in Diagnostic Approaches for Epstein–Barr Virus

“…It has been suggested that tumor necrosis factor receptors (TNFRs) might be induced by LMP1 with a higher expression of TNFR-associated factor 1 (TRAF1) observed in EBV-associated carcinomas [12]. There is increasing evidence to suggest that a high TNFR2 expression (as preferentially expressed on cancer cells and immunosuppressive cells) in a cancer microenvironment impacts cancer progression, metastasis, and immune evasion [13,14]. Additionally, circular RNAs (circRNAs), a unique class of conserved non-coding RNA, have been found to play a vital role in EBV latency and the reactivation of B lymphocytes and epithelial cells into several EBV-associated carcinomas [11,15].…”

Biomarkers for Temporomandibular Disorders: Current Status and Future Directions

“…Inflammation is prevented by the suppressive Tregs as the inflammatory cells are suppressed and the tolerogenic dendritic cells (DCs) are induced by the suppressive MDSCs, allowing the suppression of inflammation manifestations [109]. Figure 2 presents a complete description of the implication of TNFR2 activation in building immunosuppressive cells [110]. Figure 2.…”

“…However, the Etk, through the PI3K/Akt pathway, is able to activate both AP1 and MAPK signalling pathways, which activate the promoter of proliferation, survival and other transcription factors. Further, it is associated with enhancing the phosphorylation of signal transducer and activator of transcription 5 (STAT5) that play a crucial role in immunosuppression (Adopted from Al-Hatamleh et al, 2019 [110]).…”