Immune dysfunction may contribute to tumor progression in gastric cancer (GC) patients. One mechanism of immune dysfunction is the suppression of T cell activation and impairment of the efficacy of cancer immunotherapy by myeloid-derived suppressor cells (MDSCs). We assessed the phenotype and immunosuppressive function of MDSCs in GC patients. We further investigated the role of S100A8/A9 in GC and the relationship between S100A8/A9 and MDSC function. Lastly, the effect of MDSCs on survival rates and its potential as a prognostic factor in GC patients were investigated. MDSCs from PBMCs of GC patients were identified by comparing the expression of specific surface markers with PBMCs from healthy individuals. The ability of MDSCs to suppress T lymphocyte response and the effect of S100A8/A9 and RAGE blocking were tested in vitro by (autologous) MLR. GC patients had significantly more MDSCs than healthy individuals. These MDSCs suppressed both T lymphocyte proliferation and IFN-γ production and had high arginase-I expression. Levels of S100A8/A9 in plasma were higher in GC patients compared with healthy individuals, and they correlated with MDSC levels in the blood. Blocking of S100A8/A9 itself and the S100A8/A9 receptor RAGE on MDSCs from GC patients abrogated T cell effector function. We found that high levels of MDSCs correlated with more advanced cancer stage and with reduced survival (p = 0.006). S100A8/A9 has been identified as a potential target to modulate antitumor immunity by reversing MDSC-mediated immunosuppression.

This study aimed to examine effects of short- or long-term acclimation to brackish water or seawater on the climbing perch, Anabas testudineus, which is an aquatic air-breathing teleost living typically in freshwater. A. testudineus exhibits hypoosmotic and hypoinoic osmoregulation; the plasma osmolality, [Na+] and [Cl-] of fish acclimated to seawater were consistently lower than those of the external medium. However, during short-term (1 day) exposure to brackish water (15 per thousand) or seawater (30 per thousand), these three parameters increased significantly. There were also significant increases in tissue ammonia and urea contents, contents of certain free amino acids (FAAs) in the muscle, and rates of ammonia and urea excretion in the experimental fish. The accumulated FAAs might have a transient role in cell volume regulation. In addition, these results indicate that increases in protein degradation and amino acid catabolism had occurred, possibly providing energy for the osmoregulatory acclimation of the gills in fish exposed to salinity stress. Indeed, there was a significant increase in the branchial Na+/K+ -ATPase activity in fish exposed to seawater for a prolonged period (7 days), and the plasma osmolality, [Na+] and [Cl-] and the tissue FAA contents of these fish returned to control levels. More importantly, there was a significant increase in the dependence on water-breathing in fish acclimated to seawater for 7 days. This suggests for the first time that A. testudineus could alter its bimodal breathing pattern to facilitate the functioning of branchial Na+/K+ -ATPase for osmoregulatory purposes.

Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan–Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8–78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need.

Study Objective: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

TPS542 Background: In recent years, Yttrium-90 (Y90) trans-arterial radioembolization (TARE) has emerged as a therapeutic option for intermediate stage hepatocellular carcinoma (HCC). Cancer immunotherapy targeting tumour immune evasion has shown remarkable successes in various cancers. Nivolumab, an immune checkpoint inhibitor of programmed death 1 (PD1), has demonstrated encouraging activity in advanced stage HCC. Similarly, chronic hepatitis B virus (HBV) infection, a strong risk factor for HCC, is characterized by immune escape mechanisms. We hypothesize that TARE will stimulate tumor and/or HBV specific T cell responses that can be boosted using nivolumab. We thus propose an open label phase 2 trial investigating the combination of TARE with nivolumab in BCLC intermediate stage HCC. Methods: Eligible patients (pts) have ECOG performance status ≤ 2, Child-Pugh A score, intermediate stage HCC planned for TARE according to institutional practice with adequate organ function. Pts will be treated with TARE followed by nivolumab 240mg, 21 days after TARE and every 2 weeks thereafter. Pre- and on-treatment tumor biopsies will be taken. Primary end-point is response rate (RR) of combinational TARE and nivolumab. Key secondary end points are: progression free survival, overall survival, safety and quality of life using FACT-HEP score and EORTC QLQ-C30. Exploratory objectives are to evaluate how tumor PD L-1 expression, HCC mutational burden and blood lymphocyte activation/phenotypic profiles correlate with tumor response. Where possible, serial changes in antigen-specific T cell responses to HBV and/or tumour antigens will also be assessed. This study aims to enroll 40 pts as calculated using the Simon two-stage optimal design with 80% power and one sided significance level of 0.05. This will assess whether the addition of nivolumab improves the RR of TARE at 8 weeks from 21% to 41%. Patient accrual was initiated in December 2016 and as of September 2017, 9 pts have been treated. Clinical trial information: 03033446.