Figure 5 - available via license: Creative Commons Attribution 4.0 International
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Mn 2+ as an activator of the cGAS-STING pathway. Abbreviations: cGAS-cGAMP synthase; IFI16-interferon γ-inducible protein 16; DDX41-helicase DEAD box polypeptide 41; c-di-GMP-cyclic di-GMP; c-di-AMP-cyclic di-AMP; STING-stimulator of interferon genes; IRF3-interferon (IFN) regulatory factor 3; TBK1-TANK-binding kinase 1; cGAMP-cyclic guanosine monophosphate-adenosine monophosphate; DAI-DNA-dependent activator of IRFs; IFNs-type-I interferons; STING (also known as MITA, MPYS, or ERIS); cGAMP-cyclic GMP-AMP; and IRF3-IFN-regulatory factor 3.
Source publication
Immunotherapy is among the most effective approaches for treating cancer. One of the key aspects for successful immunotherapy is to achieve a strong and stable antitumor immune response. Modern immune checkpoint therapy demonstrates that cancer can be defeated. However, it also points out the weaknesses of immunotherapy, as not all tumors respond t...
Contexts in source publication
Context 1
... 2+ have recently been shown to be activators of the cGAS-STING pathway [73,184] (see Figure 5). It has been proven to play critical roles in the initiation of cancer immunity, ameliorating the immunosuppressive network in "cold" tumors [185]. ...
Context 2
... a completed phase 1 clinical trial with the combined regimen of Mn 2+ and anti-PD-1 antibodies showed promising efficacy [73] [73]. Figure 5. Mn 2+ as an activator of the cGAS-STING pathway. ...
Context 3
... recent years, many STING agonists have been identified and applied to preclinical or clinical trials for the purposes of cancer immunotherapy [244]. The STING pathway is activated by cyclic dinucleotides (CDNs), as is shown in Figure 5. However, CDN-mediated STING activation therapy with LMW compounds is limited by low bioavailability and poor cellular permeability, as well as other adverse effects [245,246]. ...
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Graphical abstract
Malignant tumors have a unique tumor microenvironment (TME), which includes mild acidity, hypoxia, overexpressed reactive oxygen species (ROS), and high glutathione (GSH) levels, among others. Recently, TME regulation approaches have attracted widespread attention in cancer immunotherapy. Nanoparticles as drug delivery systems have ability to modulate the hydrophilicity of drugs to affect drug uptake and efflux in tumor. Especially, the metal nanoparticles have been extensive applied for tumor immunotherapy due to their unique physical properties and elaborate design. However, the potential deficiencies of metal nanoparticles due to their low biodegradability, toxicity and treatment side effects restrict their clinical application. In this review, we briefly introduce the feature characteristics of the TME and the recent advances in tumor microenvironment responsive metal nanoparticles for tumor immunotherapy. In addition, nanoparticles could be combined with other treatments, such as chemotherapy, radiotherapy and photodynamic therapy also is presented. Finally, the challenges and outlook for improving the antitumor immunotherapy efficiency, side effect and potential risks of metal nanoparticles has been discussed.
