Contactin-4 suppresses antitumor T cell responses by engaging amyloid precursor protein.

Immune checkpoint inhibitors have substantial advanced tumor treatment, but their limited benefits and strong responses in only a subset of patients remain challenging. In this study, we explored the immunomodulatory function of contactin-4 (CNTN4). CNTN4 was highly expressed in tumor tissues, and expression impaired the antitumor function of T cells. CNTN4 bound to amyloid precursor protein (APP) on T cells, which attenuated conjugation between cancer cells and T cells, and diminished T cell receptor signaling cascades. We developed an anti-CNTN4 antibody (GENA-104A16) and an anti-APP antibody (5A7) that blocked the binding between CNTN4 and APP. Administration of either GENA-104A16 or 5A7 promoted antitumor T cell responses in a syngeneic mouse model and increased tumor-infiltrating lymphocytes in vivo. Furthermore, elevated CNTN4 levels were associated with poor prognosis and negatively correlated with various cytotoxic immune-related markers. These results suggest that CNTN4-APP is an inhibitory checkpoint in T cells and represents a promising therapeutic strategy for cancer immunotherapy.

The relationship between the fish consumption and blood total/methyl-mercury concentration of costal area in Korea.

The purpose of this study was to evaluate the relationship between fish consumption and blood THg/MeHg concentration in Korean adults by measuring MeHg concentration in blood directly. The study subjects consisted of 400 adults aged 20 or older from 30 subareas in Busan, Ulsan and Gyeongsangnam-do province in Korea from August to October, 2010. We tried to recruit the same number of male and female participants in different age groups (20s, 30s, 40s, 50s and 60s) and allocated 13-16 subjects by district to represent Hg concentration in the research areas. The geometric means of THg and MeHg concentration in blood were 5.27 µg/L (5.00-5.57) and 4.05 µg/L (3.81-4.32), respectively. The proportion of MeHg/THg concentration was 78.53% (77.09-79.97). MeHg concentration was higher in coastal areas (4.26 µg/L) than in inland areas (3.52 µg/L) and was higher in men (4.68 µg/L) than in women (3.52 µg/L). In male participants, blood MeHg concentration increased with increasing annual fish consumption, and the proportion of MeHg/THg concentration showed an upward trend as THg concentration increased. However, none of the measures of the proportion of MeHg/THg showed significant differences. This is the first report in Korea about the relationship between blood MeHg concentration and related factors. Our findings suggest that MeHg concentration is affected by fish consumption as well as by gender difference and drinking status. Since the pathological mechanism has not been clarified, additional studies are needed for explaining the biological and lifestyle differences in the risk of adverse health effects by Hg exposure.

Analysis of methylmercury concentration in the blood of Koreans by using cold vapor atomic fluorescence spectrophotometry.

BACKGROUND: Methylmercury is an organic form of mercury that is highly toxic to humans. Here, we present and establish a novel method to detect methylmercury concentrations in the blood of Koreans. METHODS: Methylmercury concentration was analyzed with an automated methylmercury analytic system (MERX, Brooks Rand Co., USA) using cold vapor atomic fluorescence spectrophotometry (CVAFS). A variety of biological materials were digested in methanolic potassium hydroxide solution. The analysis method was validated by examination of certified reference material (955c, National Institute of Standard and Technology, USA). We randomly selected 30 Korean adults (age 20 yr or older) to analyze total blood mercury and methylmercury concentrations. RESULTS: The detection limit and methylmercury recovery rate using this method were 0.1 pg/L and, 99.19% (range: 89.33-104.89%), respectively. The mean blood concentration of methylmercury was 4.54±2.15 µg/L (N=30). The mean proportion of methylmercury to the total mercury concentration was 78.27% (range: 41.37-98.80%). CONCLUSIONS: This study is the first report to analyze blood methylmercury concentration using CVAFS in Korea. We expect that this method will contribute to the evaluation of mercury exposure and the assessment of the toxicological impact of mercury in future studies.