A new discovery of highly hierarchical fibrillar biogenic silica with mesoporous structure derived from the perennial plant Equisetum f luviatile was made. By removing the organic compounds through chemical and heat treatment, the biogenic silica skeleton can largely retained the original highly hierarchical structure of the plant stems. Infrared spectra, X-ray diffraction, and small-angle X-ray scattering, as well as nitrogen sorption analysis, were employed to characterize the crystalline phases, nanostructure, and porosity of the resulting material. Scanning electron microscopy and transmission electron microscopy investigation reveal that the biogenic silica are fibers with diameters of about 120−150 μm and lengths of more than a few centimeters. These fibers consist of smaller fasciculus with diameters of about 5−15 μm that are composed of three levels of particles with mass and surface fractal characteristics: primary particles on the order of 3−5 nm, secondary particles on the order of 9−12 nm, and tertiary particles on the order of 90−120 nm in size. It is also shown that the biogenic silica have mesoporous structure with an average pore size of 4−6 nm and a specific surface of 100−300 m 2 /g. Heat treatment at high temperature and residual K + significantly affects the characteristics of the mesoporous structure of the biogenic silica, although it has little effect on the surface fractal structure of the secondary particles.
Introduction
Programmed cell death 1 ligand 1 (PD-L1) can be upregulated in cancer cells via interferon gamma (IFNγ) in the tumor microenvironment. IFNγ/PD-L1 signaling is associated with the response to immune checkpoint blockade in melanoma patients. Our previous investigation indicated that the microsatellite instability-high (MSI-H) cell line might exhibit selective hyperresponsiveness to IFNγ treatment, which contributes to increased PD-L1 expression and may be a mechanism of response to anti-PD-1 therapy in colorectal cancer.
Methods
The present study evaluated the expression of PD-L1 in a set of MSI and microsatellite stability (MSS) cell lines with IFNγ treatment. The differential signaling molecules associated with signal transducer and activator of transcription (STAT) contributing to hyperresponsiveness to IFNγ exposure were also investigated. Furthermore, we established a coculture assay containing CT26 cells with higher expression of PD-L1 and peripheral blood mononuclear cells (PBMCs) in vitro. Changes in cancer cell viability as well as apoptosis status in response to anti-PD-1 therapy were demonstrated. We further observed changes in the percentage of CD4
+
and CD8
+
lymphocytes after PD-1 immunotherapy in the coculture assay. Finally, the average extent of inflammation and adaptive immunity factors in the assay was also investigated.
Results
This in vitro study revealed that the MSI cell line might exhibit hyperresponsiveness to IFNγ exposure, and IFNγ induced upregulation of PD-L1 mainly through increased STAT1 and decreased STAT3 signaling. IFNγ/PD-L1 signaling participated in the response to anti-PD-1 therapy mainly through the CTL profile.
Discussion
Our findings reinforce previous knowledge of the fact that the response to immune checkpoint blockade occurs mainly in patients with a preexisting intratumoral IFNγ/PD-L1 signal, thus suggesting potential therapeutic strategies to enhance responsiveness to PD-1 blockade immunotherapy in most patients with colorectal cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.