ARID1A deficiency in EBV-positive gastric cancer is partially regulated by EBV-encoded miRNAs, but not by DNA promotor hypermethylation

博士（医学）福島県立医科大

ANALYSIS OF CELL-SURVIVAL FRACTIONS FOR HEAVY-ION IRRADIATIONS BASED ON MICRODOSIMETRIC KINETIC MODEL IMPLEMENTED IN THE PARTICLE AND HEAVY ION TRANSPORT CODE SYSTEM

It is considered that the linear energy transfer (LET) may not be the ideal index for expressing the relative biological effective- ness (RBE) of cell killing for heavy-ion irradiation, as the ion-species dependencies have clearly been observed in the relation between LET and RBE derived from cell-survival fraction data. The previously measured survival fractions of four cell lines irra- diated by various ion species, employing the saturation-corrected dose-mean lineal energy, y*, instead of LET as the index of the RBE were therefore re-analysed. In the analysis, the initial slopes of the survival fractions, the so-called a-parameter in the linear-quadratic model, were plotted as a function of y*, which was calculated by the microdosimetric kinetic (MK) model implemented in the Particle and Heavy Ion Transport code System. It was found from the analysis that the ion-species depen- dencies observed in the relations between a and LET disappeared from those between a and y*, and their relations can be well reproduced by a simple equation derived from the MK model. These results clearly indicate the suitability of y* to be used in the estimation of the RBE of cell killing for heavy-ion irradiations, which is of great importance in the treatment planning of charged-particle therapy

Tn Antigen Expression Defines an Immune Cold Subset of Mismatch-Repair Deficient Colorectal Cancer

Colorectal cancer (CRC) cells often express Tn antigen, a tumor-associated truncated immature O-glycan (GalNAcα-O-Ser/Thr) that can promote tumor progression. Immunotherapies against Tn antigen have been developed and are being evaluated in clinical trials. Tn antigen can also be considered a novel immune checkpoint that induces immunosuppressive signaling through glycan-biding lectins to lead effector T cell apoptosis. We evaluated the correlation of Tn antigen expression by immunohistochemistry with mismatch-repair (MMR) status, tumor-infiltrating lymphocytes, tumor cell PD-L1 expression, and clinicopathological characteristics in 507 CRC patients. Although 91.9% of CRCs showed negative or weak Tn antigen staining (Tn-negative/weak), we identified a small subset of CRCs (8.1%) that displayed particularly intense and diffuse distribution of Tn antigen immunoreactivity (Tn-strong) that closely related to deficient MMR (dMMR). Moreover, 40 dMMR CRCs were stratified into 24 Tn-negative/weak dMMR tumors (60.0%) exhibiting dense CD8+ lymphocyte infiltrate concomitant with a high rate of PD-L1 positivity, and 16 Tn-strong dMMR tumors (40.0%) that demonstrated CD8+ T cell exclusion and a lack of PD-L1 expression, which was comparable to those of proficient MMR. Our finding suggests that the immune cold subset of patients with Tn-strong dMMR CRC may be effectively treated with immune checkpoint blockade therapy or cellular immunotherapy targeting Tn antigen