Abstract
Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT.
Highlights
In recent years, immunotherapy has gained interest as an option in cancer treatment
transmission electron microscopy (TEM) images showed that the mesoporous silica nanoparticles (MSNs) had a spherical mesoporous structure (Figure 1A)
The antigen-capturing capacity of MSNs was estimated by the adsorption of fluorescein-conjugated ovalbumin (F-OVA)
Summary
Immunotherapy has gained interest as an option in cancer treatment. Immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4(CTLA-4), programmed cell death protein 1 (PD1), and programmed cell death ligand 1(PD-L1) have been approved by the United States Food and Drug Administration (FDA)and are considered promising systemic therapies based on clinical trials for various types of cancers [1]. Immunotherapy has gained interest as an option in cancer treatment. Immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated protein 4. Are considered promising systemic therapies based on clinical trials for various types of cancers [1]. Radiotherapy (RT) is one of the major types of cancer treatments and is known to modulate cancer immunity. Preclinical studies and some clinical cases have reported surprising results of the abscopal effect of combining immunotherapy with RT [2]. This has not yet become standard treatment in the clinic, and not all patients have experienced this positive outcome. Clinical trials to determine the optimal combination of RT and immunotherapy are ongoing
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