Difference between Keratinized- and Non-Keratinized-Originating Epithelium in the Process of Immune Escape of Oral Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.

Biomimetic mineralization using matrix vesicle nanofragments.

In vitro synthesis of bone tissue has been paid attention in recent years; however, current methods to fabricate bone tissue are still ineffective due to some remaining gaps in the understanding of real in vivo bone formation process, and application of the knowledge in bone synthesis. Therefore, the objectives of this study were first, to perform a systematic and ultrastructural investigation of the initial mineral formation during intramembranous ossification of mouse calvaria from a material scientists' viewpoint, and to develop novel mineralization methods based on the in vivo findings. First, the very initial mineral deposition was found to occur at embryonic day E14.0 in mouse calvaria. Analysis of the initial bone formation process showed that it involved the following distinct steps: collagen secretion, matrix vesicle (MV) release, MV mineralization, MV rupture, and collagen fiber mineralization. Next, we performed in vitro mineralization experiments using MVs and hydrogel scaffolds. Intact MVs embedded in collagen gel did not mineralize, whereas, interestingly, MV nanofragments obtained by ultrasonication could promote rapid mineralization. These results indicate that mechanically ruptured MV membrane can be a promising material for in vitro bone tissue synthesis. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1021-1030, 2019.