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Abstract
Dendritic cells (DCs) are the most effective type of antigen-presenting cells (APCs). DCs capture tumor antigens, process them, and migrate to the T cell zone in tumor-draining lymph nodes (TDLNs) where they prime naïve T cells through cross-presentation. During this process, DCs manifest upregulated antigen-presenting molecules (major histocompatibility complexes MHC-I and MHC-II) and co-stimulatory molecules (CD80, CD86 and CD40), and elevated secretion of cytokines such as interleukin 12 (IL-12) and tumor necrosis factor-α (TNF-α). After cross-presentation, naïve T cells proliferate and differentiate into effective CD8+ cytotoxic T lymphocytes (CTLs) and CD4+ helper T lymphocytes (TH cells). These effective T cells travel back to tumors where CD8+ CTLs kill cancer cells in an antigen-specific manner and CD4+ TH cells secrete cytokines to attract other immune cells to the site. However, tumor microenvironment (TME) is rich in immunosuppressive factors, which may suppress DC maturation and migration thus curbing T cell immunity. Many have explored immune modulators that can stimulate DCs to boost immune responses. Despite the progress, however, selectively and safely activating DCs in vivo remain elusive. DC responses are largely governed by Ca2+ signaling. During maturation, intracellular calcium of DCs is elevated, triggering signaling cascades that result in upregulation of co-stimulatory and antigen-presenting molecules. Herein, we investigate calcium nanoparticles as a novel type of immune modulator for DCs. We postulate that calcium nanoparticles taken up by DCs can slowly release calcium therein, thus promoting DC maturation, migration, and cross-presentation, in turn augmenting T cell immunity against cancer.