Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors

IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method

Radiation survey along two trails in Mt. Fuji to investigate the influence of the radioactive contamination due to the Fukushima nuclear accident

Mt. Fuji is located approximately 300 km southwest of the Fukushima Daiichi Nuclear Power Stations. We performed the radiation survey along two main Mt. Fuji\u27s trails from 4:30 to 18:30 on July 9, 2011. We climbed the Yoshida trail from the Fuji-Subaru Line fifth station (2,300 m in altitude) to the Yoshida-Subashiri top (3,720 m in altitude) and descended the Subashiri trail from the Yoshida-Subashiri top to the Subashiri new fifth station (2,000 m in altitude) on foot while measuring gamma rays. The dose rate 1 m above ground measured using a NaI (Tl) scintillation survey meter were within the range from 0.03 µSv/h to 0.05 µSv/h throughout our measuring trip. We used a NaI (Tl) scintillation spectrometer for gamma-ray pulse height spectra measurement. The gamma-ray pulse height spectra obtained at least 2,500 m in altitude on both of the Yoshida and Subashiri trail showed the peaks of two radioactive cesium isotopes (Cs-134 and Cs-137) and natural radioactive nuclides. It was confirmed that a radioactive plume released from the Fukushima Daiichi Nuclear Power Stations had arrived at least 2,400m above sea level of Mt. Fuji.International Symposium on Environmental monitoring and dose estimation of residents after accident of TEPCO\u27s Fukushima Daiichi Nuclear Power Station

Survey of Radioactive Contamination along Mt. Fuji\u27s Climbing Routes Following TEPCO\u27s Fukushima Daiichi Nuclear Power Plant Accident

TEPCO’s Fukushima Daiichi Nuclear Power Plant (FDNPP) accident occurred in March 2011, and the resulting release of radioactive nuclides contaminated Mt.Fuji’s ground surface. It was of great concern that climbers would be at a risk of being exposed to elevated radiation levels at Mt. Fuji. In this study, dose rates in air (absorbed dose rates in air) were continuously measured while climbing along two popular climbing routes: the Yosida (Kawaguchiko) and Subashiri routes. The dose rates ranged from 15 to 24 nGy/h, which are less than the background level for terrestrial gamma rays in Japan (51 nGy/h). This study suggests that the deposition of artificial radioactive nuclides over the Mt. Fuji and its climbing routes has little effect on the increase of the dose rates in air