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Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)‐interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING‐IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV‐1‐based OV, C‐REV, with a membrane‐impermeable STING agonist, 2′3′‐GAMP. Our results demonstrated that tumor cells harbor a largely defective STING‐IFN pathway, thereby preventing significant antiviral IFN induction regardless of the permeability of the STING agonist. In vivo, the combination therapy induced more proliferative KLRG1‐high PD1‐low CD8+ T‐cells and activated CD103+ DC in the tumor site and increased tumor‐specific CD44+ CD8+ T‐cells in the lymph node. Overall, the combination therapy of C‐REV with 2′3′‐cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non‐treated distal tumors.

Abstract Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, l-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.

Sprint performance plays a crucial role in various sports. Short sprints vary depending on the size of the court/playing field and on competitive characteristics, but are common in many sports. Although the relationship between age and muscle strength has been explored in short sprints, there is limited understanding of how various physical factors interact, particularly concerning differences in the acceleration phase. This study examined the relationship between sprint times at 0–2.5 m, 2.5–5 m, and 5–10 m intervals and various factors (body composition, flexibility, muscle strength, physical fitness) in junior athletes (13 boys; 13 girls; average age 11.37 ± 1.30 years; 7 in badminton, 8 in fencing, 5 in rowing, and 6 in climbing). The sprint time was measured using four timing lights at 0 m (start point), 2.5 m, 5 m, and 10 m (finish point). The results indicated that sprint times increased with age, and is correlated with muscle strength and flexibility. A partial correlation analysis showed that faster times in the 0–2.5 m interval were associated with higher hip flexibility (right: r = −0.42, p = 0.035; left: r = −0.60, p = 0.001); in the 2.5–5 m interval, faster times were associated with higher core flexibility (right: r = −0.34, p = 0.091; left: r = −0.40, p = 0.046); and in the 5–10 m interval, a relationship with standing long jump performance was confirmed (r = −0.56, p = 0.003). Furthermore, a lower fat-free body weight translated to higher performance (0–2.5 m: r = 0.40, p = 0.047; 2.5 m: r = 0.37, p = 0.071; 5–10 m: r = 0.55, p = 0.004). In the acceleration phase of 10 m, flexibility immediately after the start and the subsequent horizontal propulsive force are important factors that are strongly related to performance change in each interval. These results emphasize that even over a short distance such as 10 m, the factors influencing performance can change significantly. This highlights the importance of overall flexibility, propulsive power and body fat regulation in junior short sprinters, as well as the need for daily training carefully tailored to the specific sprint distances required in each sport.

Abstract Oncolytic virus (OV) therapy is a promising cancer immunotherapy, especially for cold tumors by inducing the direct lysis of cancer cells and initiation of potent antitumor response. Canerpaturev (C-REV) is an attenuated oncolytic herpes simplex virus-1, which demonstrated a potent antitumor effect in various preclinical models when used either alone or combined. Metformin is a commonly prescribed antidiabetic drug that demonstrated a potent immune modulator effect and antitumor response. We combined C-REV with metformin in a low immunogenic bilateral murine tumor model to enhance C-REV’s antitumor efficacy. In vitro, metformin does not enhance the C-REV cell cytotoxic effect. However, in in vivo model, intratumoral administration of C-REV with the systemic administration of metformin led to synergistic antitumor effect on both sides of tumor and prolonged survival. Moreover, combination therapy increased the effector CD44+ CD8+ PD1- subset and decreased the proportion of terminally-differentiated CD103+ KLRG-1+ T-regulatory cells on both sides of tumor. Interestingly, combination therapy efficiently modulates conventional dendritic cells type-1 (cDC1) on tumors, and tumor-drained lymph nodes. Our findings suggest that combination of C-REV and metformin enhances systemic antitumor immunity. This study may provide insights into the mechanism of action of OV therapy plus metformin combination against various tumor models.

Abstract Aim We conducted a scoping review of nursing ethics education to examine educational formats that go beyond traditional lectures. Design This study was a scoping review. Methods We used seven databases and relevant search terms, including nursing ethics, morals, values, nursing students and nursing ethics education. Results Of 5,190 papers, 14 quasi‐experimental studies met the inclusion criteria. All papers examined practices and self‐study added to traditional lecture styles (i.e. the control group). Five practices emerged as follows: combined web (i.e. Internet) and lecture, web‐based self‐study, simulation, group learning and analysing ethical issues. The purpose, method and evaluation method differed based on the country in which the study was conducted. These educational interventions yielded significant differences in knowledge and in nursing students' critical thinking and ethical sensitivity postintervention. Multi‐faceted ethics education will lay the foundation for effective practical training and practice.

Abstract Background The school environment provides crucial opportunities for children to engage in health-promoting physical activity (PA). Japanese children clean their schools and have recess time every school day. The primary aim of the study is to describe the levels of physical activity during school cleaning and recess time while comparing it between genders. Methods PA and sedentary behavior (SB) of 230 boys and 252 girls aged 6–12 years-old from 14 public primary schools were assessed for 7 consecutive days with a triaxial accelerometer. Minutes of SB, and moderate-to-vigorous PA (MVPA) as a percentage in each of school cleaning time (15 min/day: 58% of the 14 schools or 20 min/day), morning recess time (15 min/day: 6% or 20 min/day) or lunch recess time (15 min/day: 29%, 20 min/day: 47% or 25 min/day) were evaluated. A one-way analysis of variance or Student’s t test was used to examine differences in %PAs and %SB between school cleaning time and morning and lunch recess time, and between genders. Results In a school day, the percentage of total daily MVPA during school cleaning time, morning recess and lunch recess time was 19.4 ± 6.8% (15.2 ± 5.3 min/day) for boys and 16.9 ± 5.8% (10.5 ± 4.3 min/day) for girls. For boys, the proportions of MVPA in morning and lunch recesses and SB during the morning recess were significantly higher than during school cleaning time (p

The naturally occurring oncolytic herpes simplex virus canerpaturev (C-REV), formerly HF10, proved its therapeutic efficacy and safety in multiple clinical trials against melanoma, pancreatic, breast, and head and neck cancers. Meanwhile, patients with colorectal cancer, which has increased in prevalence in recent decades, continue to have poor prognosis and morbidity. Combination therapy has better response rates than monotherapy. Hence, we investigated the antitumor efficacy of cetuximab, a widely used anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and C-REV, either alone or in combination, in vitro and in an in vivo human colorectal xenograft model. In human colorectal cancer cell lines with different levels of EGFR expression (HT-29, WiDr, and CW2), C-REV exhibited cytotoxic effects in a time- and dose-dependent manner, irrespective of EGFR expression. Moreover, cetuximab had no effect on viral replication in vitro. Combining cetuximab and C-REV induced a synergistic antitumor effect in HT-29 tumor xenograft models by promoting the distribution of C-REV throughout the tumor and suppressing angiogenesis. Application of cetuximab prior to C-REV yielded better tumor regression than administration of the drug after the virus. Thus, cetuximab represents an ideal virus-associated agent for antitumor therapy, and combination therapy represents a promising antitumor strategy for human colorectal cancer. Keywords: HSV, cetuximab, oncolytic herpes virus HF10, C-REV, human colorectal cancer

Background: Several studies have investigated the association between benzodiazepine receptor agonist (BZDRA) use during the perioperative period and an elevated incidence of delirium. However, no study has focused on the time course of BZDRA use, including continuation, discontinuation, initiation, and no use. This study aimed to examine the influence of the time course of BZDRA use on post-operative delirium. Methods: This retrospective cohort study was conducted by reviewing medical records. We included patients who were scheduled for surgery under general anesthesia and had been referred to a liaison psychiatrist for pre-operative psychiatric assessment. The patients were classified into four groups based on the pre- and post-operative time course of oral BZDRA use, as follows: continuation, discontinuation, initiation, and no use (never used). The primary outcome was the prevalence of post-operative delirium in non-intensive care unit settings. We also performed stratified analyses according to age, the presence of cognitive impairment, the presence of delirium history, and antipsychotic drug use on admission. Results: Among 250 patients, 78 (31%) developed post-operative delirium. The Discontinuation group had a higher rate of delirium (49%, 24/49) than the other groups (Continuation [14%, 4/29]; Initiation [38%, 3/8], Never used [29%, 47/164], p = 0.008). Conclusions: Abrupt discontinuation of BZDRAs during the perioperative period may be a risk factor for post-operative delirium and should therefore be avoided.

Abstract Background During the typical school day, physical education (PE) gives children an opportunity for physical activity (PA) and reduces their sedentary time, but little is known about objectively evaluated PA and sedentary time during PE lessons and the differences across genders and grades. There is also a lack of research comparing PA and sedentary time among the different types of PE lessons. The primary aim of this study was to examine primary school students’ moderate-to-vigorous PA (MVPA) levels and sedentary time during PE and whether there are gender or grade differences in a cross-sectional study. The secondary aim was to determine which types of PE lessons are best for increasing PA and reducing sedentary time. Methods Objectively evaluated MVPA and sedentary time during PE lessons in Japan with a triaxial accelerometer (Active style Pro HJA-350IT, Omron Healthcare) in girls (n = 221) and boys (n = 181). Minutes of sedentary time were categorized into metabolic equivalents (METs): categories ranged from sedentary time (METs ≤1.5) to MVPA (METs ≥3.0). Time tables and PE lesson types were evaluated using logs maintained by the class teachers. Results Time spent in MVPA and sedentary time were 27.3 and 24.3%, respectively. After adjustments for grade, relative body weight and school, boys spent significantly more time in MVPA compared with girls, but with an estimated mean difference of approximately 1 min. After adjustment for gender, relative body weight and school, the younger grades (1st and 2nd) spent significantly more time in MVPA and significantly less time in sedentary time compared with other grades. Moreover, after adjustments for gender, grade, relative body weight and school, the time spent in MVPA during gymnastic and track and field lessons was significantly lower than that during ball game lessons. Sedentary time during gymnastic lessons was significantly longer than in track and field and ball game lessons. Conclusions Children did not engage in much MVPA and also spent time in sedentary time during PE, but there are no gender differences. The children were most active during ball game lessons. Therefore, it is important to increase MVPA and reduce sedentary time during PE in both genders.

Abstract Background Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study. Methods This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment. Results Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR). Conclusions HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies. Trial registration: This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013.

Patients who undergo surgical extirpation of a primary liver carcinoma followed by radiotherapy and chemotherapy leading to complete remission are nevertheless known to develop cancerous metastases 3–10 years later. We retrospectively examined the blood sera collected over 8 years from 30 patients who developed bone metastases after the complete remission of liver cancer to identify serum proteins showing differential expression compared to patients without remission. We detected a novel RGD (Arg-Gly-Asp)-containing peptide derived from the C-terminal portion of fibrinogen in the sera of metastatic patients that appeared to control the EMT (epithelial-mesenchymal transition) of cancer cells, in a process associated with miR-199a-3p. The RGD peptide enhanced new blood vessel growth and increased vascular endothelial growth factor levels when introduced into fertilized chicken eggs. The purpose of this study was to enable early detection of metastatic cancer cells using the novel RGD peptide as a biomarker, and thereby develop new drugs for the treatment of metastatic cancer.

Abstract Background Even when meeting guidelines for physical activity (PA), considerable sedentary time may be included. This study in primary school children investigated the relationships between objectively evaluated sedentary and PA times at different intensities using triaxial accelerometry that discriminated between ambulatory and non-ambulatory PA. The relationships between subjectively evaluated screen time (i.e. time spent viewing television and videos, playing electronic games, and using personal computers) and objectively evaluated sedentary and PA times were examined. Methods Objectively evaluated sedentary and PA times were assessed for 7 consecutive days using a triaxial accelerometer (Active style Pro: HJA-350IT) in 426 first to sixth grade girls and boys. Metabolic equivalents [METs] were used to categorize the minutes of sedentary time (≤1.5 METs), light PA (LPA, 1.6–2.9 METs), moderate-to-vigorous PA (MVPA, ≥3.0 METs) and vigorous PA (VPA, ≥6.0 METs). The physical activity level (PAL) was calculated using the mean MET value. Subjectively evaluated screen time behaviors were self-reported by participants and parents acting together. The associations between PA and sedentary and screen time variables were examined using partial correlation analyses. Results After adjustment for age, body weight and wearing time, objectively evaluated sedentary time correlated strongly with non-ambulatory and total LPA and PAL, moderately with ambulatory LPA, non-ambulatory or total MVPA, and weakly with ambulatory MVPA, ambulatory, non-ambulatory or total VPA. Subjectively evaluated screen time was not associated significantly with objectively evaluated sedentary and PA times or PAL. On average, each reduction of 30 min in daily sedentary time was associated with 6 or 23 min more of MVPA or LPA, respectively. Conclusions These findings show that higher daily sedentary time may be compensated mainly by lower LPA, while the association between sedentary time and MVPA was moderate. Therefore, improving MVPA and reducing sedentary time are important in primary school children.

OBJECTIVES:Quadriceps weakness (QW) following total knee arthroplasty (TKA) can be elicited by tourniquet-induced ischaemia reperfusion (IR), which causes a vigorous acute inflammatory response. Dietary n-3 polyunsaturated fatty acids (PUFA) are important determinants of organ and tissue protection from IR. This study aimed to examine the association between serum n-3 PUFA levels and QW, knee pain, and knee swelling immediately after TKA. METHODS:A total of 32 patients who underwent unilateral TKA participated in this prospective study. On Postoperative Day 1, serum n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) levels were measured. Preoperatively and on Postoperative Day 4, quadriceps strength, knee pain during quadriceps testing, and knee circumference were measured. QW, knee pain, and knee swelling were defined as changes in quadriceps strength, knee pain during quadriceps testing, and knee circumference, respectively, between the preoperative to the postoperative measurement. RESULTS:Mean serum n-3 PUFA levels were 192 μg/mL (standard deviation, 58 μg/mL) on Postoperative Day 1. All measured variables changed significantly between the preoperative and the postoperative measurement time-points (P

Oncolytic virus (OV) therapy is widely considered as a major breakthrough in anti-cancer treatments. In our previous study, the efficacy and safety of using C-REV for anti-cancer therapy in patients during stage I clinical trial was reported. The stimulator of interferon genes (STING)–TBK1–IRF3–IFN pathway is known to act as the central cellular host defense against viral infection. Recent reports have linked low expression levels of cGAS and STING in cancer cells to poor prognosis among patients. Moreover, downregulation of cGAS and STING has been linked to higher susceptibility to OV infection among several cancer cell lines. In this paper, we show that there is little correlation between levels of cGAS/STING expression and susceptibility to C-REV among human pancreatic cancer cell lines. Despite having a responsive STING pathway, BxPC-3 cells are highly susceptible to C-REV infection. Upon pre-activation of the STING pathway, BxPc-3 cells exhibited resistance to C-REV infection. However, without pre-activation, C-REV completely suppressed the STING pathway in BxPC-3 cells. Additionally, despite harboring defects in the STING pathway, other high-grade cancer cell lines, such as Capan-2, PANC-1 and MiaPaCa-2, still exhibited low susceptibility to C-REV infection. Furthermore, overexpression of STING in MiaPaCa-2 cells altered susceptibility to a limited extent. Taken together, our data suggest that the cGAS–STING pathway plays a minor role in the susceptibility of pancreatic cancer cell lines to C-REV infection.

Abstract Background The recent prevalence of obesity in Japanese children is much higher compared to 1980. The present study compared daily sedentary behavior (SB) and physical activity (PA) between the school year and summer vacation in Japanese primary school children. Methods Participants were 98 Japanese boys (8.9 ± 1.8 years at baseline) and 111 girls (9.1 ± 1.8 years). SB and PA were measured in May (school term) and July/August (summer vacation), 2011. SB and PA were assessed using a triaxial accelerometer (Active style Pro HJA-350IT, Omron Healthcare) for 7 consecutive days. The average number of minutes spent in SB (no more than 1.5 metabolic equivalents (METs)), light intensity activity (LPA; more than 1.5 to less than 3.0 METs) and moderate-to-vigorous physical activity (MVPA; 3.0 METs or more), and step counts were calculated for each individual. Moreover, the determinants/moderators of changes in SB and PA were examined. Results Daily SB was significantly higher in the summer vacation than in the school year for both boys and girls (p

OBJECTIVE:Age at onset of walking has been shown as an early predictor of physical activity in infants and children. However, little is known about whether age at onset of walking may predict sedentary behavior (SB). The aim of the present study was to examine the association between the timing of onset of walking and objectively measured SB, and whether this association is mediated by moderate-to-vigorous physical activity (MVPA) in children. METHODS:The subjects were 388 elementary school children aged 6-12 years. Current weight and height data were collected. Birth weight and the age in months the child first walked independently were reported based on the parents' recall. Children's SB and physical activity were objectively measured using a triaxial accelerometer (Active style Pro HJA-350IT, OMRON). The following summary outcome variables were derived from accelerometer data: Time (min/day) spent in SB (≤1.5 metabolic equivalents [METs]) and MVPA (≥3.0 METs). RESULTS:The mean ± SD time (min/day) spent in sedentary was 376 ± 62 and MVPA was 67.6 ± 20.8. Multiple linear regression analyses revealed that a later age at independent walking was associated with increased time spent in SB (β = 0.15, P < 0.001) and decreased time spent in MVPA (β = -0. 18, P < 0.001) after adjusting for gender, birth weight, current age, body weight, schools, and time spent wearing the accelerometer. When MVPA was introduced as a covariate in the model predicting SB, the association between the age at independent walking and time spent in SB was completely attenuated (β = 0.04, P = 0.215), while MVPA was significantly associated with SB (β = -0.61, P < 0.001). CONCLUSIONS:Our results indicate that infants who walked at a later age spent more time in SB in childhood, and this association is mediated by MVPA. Appropriate interventions which focus on increasing MVPA and thereby reducing SB may be beneficial in infants who demonstrate a later age at onset of independent walking.

Objective. We evaluated the efficacies of antimicrobial photodynamic therapy (aPDT) and minocycline ointment (MO) on clinical and bacteriological markers and the local host inflammatory response. Materials and Methods. A total of 30 patients with chronic periodontitis were randomly assigned to two groups. Selected periodontal pockets (probing depth 5–7 mm with bleeding on probing) were treated with aPDT or MO. Measurements of clinical parameters and the collection of gingival crevicular fluid (GCF) and subgingival plaque were performed at baseline, and at 1 and 4 weeks after treatment. Quantification of periodontopathic bacteria in the sulcus and a multiplex bead immunoassay of ten inflammatory cytokines in the GCF were performed. Results. Local MO administration exhibited a significant decrease in scores for clinical parameters (P

Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54. In preclinical studies, HF10 replicated efficiently within tumor cells with extensive cytolytic effects and induced increased numbers of activated CD4+ and CD8+ T cells and natural killer cells within the tumor, leading to a significant reduction in tumor growth and prolonged survival rates. Investigator-initiated clinical studies of HF10 have been completed in recurrent breast carcinoma, head and neck cancer, and unresectable pancreatic cancer in Japan. Phase I trials were subsequently completed in refractory superficial cancers and melanoma in the United States. HF10 has been demonstrated to have a high safety margin with low frequency of adverse effects in all treated patients. Interestingly, HF10 antigens were detected in pancreatic carcinoma over 300 days after treatment with infiltration of CD4+ and CD8+ T cells, which enhanced the immune response. To date, preliminary results from a Phase II trial have indicated that HF10 in combination with ipilimumab (anti-CTLA-4) is safe and well tolerated, with high antitumor efficacy. Improvement of the effect of ipilimumab was observed in patients with stage IIIb, IIIc, or IV unresectable or metastatic melanoma. This review provides a concise description of the genomic functional organization of HF10 compared with talimogene laherparepvec. Furthermore, this review focuses on HF10 in cancer treatment as monotherapy as well as in combination therapy through a concise description of all preclinical and clinical data. In addition, we will address approaches for future directions in HF10 studies as cancer therapy.

Oncolytic virotherapy combined with immunomodulators is a novel noninvasive strategy for cancer treatment. In this study, we examined the tumoricidal effects of oncolytic HF10, a naturally occurring mutant of herpes simplex virus type-1, combined with an agonistic DTA-1 monoclonal antibody specific for the glucocorticoid-induced tumor necrosis factor receptor. Two murine tumor models were used to evaluate the therapeutic efficacies of HF10 virotherapy combined with DTA-1. The kinetics and immunological mechanisms of DTA-1 in HF10 infection were examined using flow cytometry and immunohistochemistry. Intratumoral administration of HF10 in combination with DTA-1 at a low dose resulted in a more vigorous attenuation of growth of the untreated contralateral as well as the treated tumors than treatment with either HF10 or DTA-1 alone. An accumulation of CD8(+) T cells, including tumor- and herpes simplex virus type-1-specific populations, and a decrease in the number of CD4(+) Foxp3(+) T regulatory cells were seen in both HF10- and DTA-1-treated tumors. Studies using Fc-digested DTA-1 and Fcγ receptor knockout mice demonstrated the direct participation of DTA-1 in regulatory T cell depletion by antibody-dependent cellular cytotoxicity primarily via macrophages. These results indicated the potential therapeutic efficacy of a glucocorticoid-induced tumor necrosis factor receptor-specific monoclonal antibody in oncolytic virotherapy at local tumor sites.