期刊
CHEMICAL SCIENCE
卷 11, 期 28, 页码 7429-7437出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0sc00293c
关键词
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资金
- Key Research and Development Program of Shandong Province [2018YFJH0502]
- National Natural Science Foundation of China [21535004, 91753111, 21927881, 21874086, 21775094]
- National Key R&D Program of China [2019YFA0210100]
- Youth Innovation Science and Technology Program of Higher Education Institution of Shandong Province [2019KJC022]
Breast cancer recurrence is the greatest contributor to patient death. As the immune system has a long-term immune memory effect, immunotherapy has great potential for preventing cancer recurrence. However, cancer immunotherapy is often limited due to T cell activation being blocked by insufficient tumor immunogenicity and the complex immunosuppressive tumor microenvironment. Here we show a tumor acidity activatable and Ca2+-assisted immuno-nanoagent to synergistically promote T cell activation and enhance cancer immunotherapy. When the immuno-nanoagent reaches the acidic tumor microenvironment, the CaCO(3)matrix disintegrates to release immune stimulants (CpG ODNs and IDOi) and Ca2+. CpG ODNs are responsible for triggering dendritic cell maturation to increase the immunogenicity for activation of T cells. And IDOi can inhibit the oxidative catabolism of tryptophan to kynurenine for preventing T-cell anergy and apoptosis. Due to the complexity of the immunosuppressive microenvironment, it is difficult to restore T cell activation by inhibiting only one pathway. Fortunately, the released Ca(2+)can promote the activation and proliferation of T cells with the support of the immune stimulants.In vivoexperiments demonstrate that our Ca2+-assisted immuno-nanoagent can significantly suppress tumor progression and protect mice from tumor rechallenge due to the long-term memory effect. This immunotherapeutic strategy may provide more possibilities for clinical applications such as treating cancer and preventing relapse.
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