Cancer immunotherapy is a potent treatment modality, but its clinical benefit depends on the tumor's immune profile. Here, we used mJX-594 (JX), a targeted and GM-CSF-armed oncolytic vaccinia virus, ...as a strategy to remodel the tumor microenvironment (TME) and subsequently increase sensitivity to αPD-1 and/or αCTLA-4 immunotherapy.
The remodeling of the TME was determined using histologic, flow-cytometric, and NanoString immune profiling analyses. JX was intratumorally injected into implanted Renca kidney tumors or
transgenic mouse breast cancers with or without αPD-1 and/or αCTLA-4. Various combination regimens were used to evaluate immunotherapeutic anticancer responses.
Intratumoral injection of JX remodeled the TME through dynamic changes in the immune system, as shown by increased tumor-infiltrating T cells and upregulation of immune-related gene signatures. This remodeling induced conversion of a noninflamed tumor into an inflamed tumor. JX virotherapy led to enhanced abscopal effects in distant tumors, with increased intratumoral infiltration of CD8
T cells. A depletion study revealed that GM-CSF is an indispensable regulator of anticancer efficacy of JX. Dual-combination therapy with intratumoral JX and systemic αPD-1 or αCTLA-4 further enhanced the anticancer immune response, regardless of various treatment schedules. Of note, triple combination immunotherapy with JX, αPD-1, and αCTLA-4 elicited the most potent anticancer immunity and induced complete tumor regression and long-term overall survival.
Our results show that intratumoral JX treatment induces dramatic remodeling of the TME and more potently suppresses cancer progression with immune-checkpoint blockades by overcoming resistance to immunotherapy.
Oxygen functionalization of carbon supports has been a widely used strategy to enhance catalytic performance of carbon supported Pt (Pt/C) catalysts. However, the effect of oxidative ...functionalization on the catalytic performance of Pt/C catalysts for the oxygen reduction reaction (ORR) has rarely been investigated. We report the impact of oxygen functionalization of carbon black (CB) supports on the activity and durability of CB supported Pt catalysts for the ORR. Pristine and mildly oxygen-functionalized CB supported Pt catalysts (Pt/CB and Pt/CB_O, respectively) show nearly identical structural parameters, including surface areas and pore volumes of the CB support, and supported Pt particle sizes. The Pt/CB_O catalyst shows higher electrochemically active surface area and ORR activity than Pt/CB catalyst, which is likely caused by differing interfacial structure between the carbon support and Pt nanoparticles in the two catalysts. In ORR durability tests, Pt/CB exhibits significantly higher stability than Pt/CB_O. Spectroscopic characterizations reveal that oxygen functionalization in the Pt/CB_O catalyst partially oxidizes the Pt nanoparticles, triggering facile dissolution and Ostwald ripening of Pt nanoparticles, which accelerates the decline of the ORR activity of Pt CB_O.
Whether dynamic changes of metabolic syndrome (MetS) affects the subsequent laryngeal cancer occurrence remains unknown. This study investigated the effects of changes of MetS on the incidence of ...laryngeal cancer due to a lack of knowledge regarding the development of MetS in Korean population. A total of 6,757,048 individuals who received national health checkup in 2009 and follow-up health examination in 2011 were analyzed and followed up until 2018. MetS status included the following categories: MetS-chronic (n = 941,609), MetS-developed (n = 614,229), MetS-recovery (n = 455,835), and MetS-free (n = 4,745,375). With a median follow-up duration of 6.403 years, 1,350 subjects were newly diagnosed with laryngeal cancer. Compared to participants without MetS, adjusted hazard ratios (HR) (95% confidence interval) for those with MetS were 1.320 (1.17-1.489) for laryngeal cancer. The HR of laryngeal cancer was found to be increased with increasing number of MetS components. The MetS-developed group had a significantly higher risk of laryngeal cancer than the MetS-free group (HR: 1.296; 95% CI: 1.093-1.537). The MetS-recovery group within two years also had an increased risk of laryngeal cancer compared with the MetS-free group (HR: 1.220; 95% CI: 1.008-1.476). Among MetS components, abdominal obesity had the highest risk of laryngeal cancer (HR: 1.374; 95% CI: 1.123-1.681). Changes in MetS status were associated with the risk of laryngeal cancer. Results of this study have implications for etiological investigations and prevention strategies.
Among colorectal cancers (CRCs), high-frequency microsatellite instability (MSI-H) is associated with a better prognosis, compared with low-frequency MSI or microsatellite stability (MSI-L/MSS). ...However, it is unclear whether MSI affects the prognosis of recurrent CRCs.
This study included 2940 patients with stage I-III CRC who underwent complete resection. The associations of MSI status with recurrence patterns, disease-free survival (DFS), overall survival from diagnosis to death (OS1), and overall survival from recurrence to death (OS2) were analysed.
A total of 261 patients (8.9%) had MSI-H CRC. Patients with MSI-H CRC had better DFS, compared to patients with MSI-L/MSS CRC (hazard ratio (HR): 0.619, P<0.001). High-frequency microsatellite instability CRC was associated with more frequent local recurrence (30.0% vs 12.0%, P=0.032) or peritoneal metastasis (40.0% vs 12.3%, P=0.003), and less frequent lung (10.0% vs 42.5%, P=0.004) or liver metastases (15.0% vs 44.7%, P=0.01). Recurrent MSI-H CRC was associated with worse OS1 (HR: 1.363, P=0.035) and OS2 (HR: 2.667, P<0.001). An analysis of patients with colon cancer yielded similar results.
Recurrence patterns differed between MSI-H CRC and MSI-L/MSS CRC, and recurrent MSI-H CRCs had a worse prognosis.
Human papilloma virus (HPV)-related tonsil cancer is associated with favorable outcomes.
The purpose of this study was to define factors affecting distant metastasis in patients with surgically ...treated HPV-positive tonsil cancer.
The present study enrolled 76 patients diagnosed with HPV-positive tonsil cancer who underwent primary surgery between January 2010 and December 2021.
Twelve (15.7%) patients experienced a distant failure with a median follow-up time of 43 months. Sites of distant metastasis included the lung (n = 10), liver (n = 1), and brain (n = 1). Upon multivariate analysis, an advanced T stage (odds ratio OR: 13.94, 95% confidence interval CI: 1.29-149.863, p = 0.003) and margin involvement (OR: 5.96, 95% CI: 1.33-26.76, p = 0.02) were independent predictors of distant metastases. The five-year disease-specific survival for the entire cohort was 85%. The multivariate analysis confirmed that distant metastasis (hazard ratio HR: 12.688, 95% CI: 3.424-47.016; p < 0.001) and margin involvement (HR: 6.243; 95% CI: 1.681-23.191; p = 0.006) were significant factors associated with the five-year disease-specific survival.
HPV-positive tonsil cancer patients with an advanced T stage and a positive surgical margin have a substantial risk of distant metastases. Distant metastasis and margin involvement are factors that affect their survival.
The inability to guide the nucleation locations of electrochemically deposited Li has long been considered the main factor limiting the utilization of high‐energy‐density Li‐metal batteries. In this ...study, an electrical conductivity gradient interfacial host comprising 1D high conductivity copper nanowires and nanocellulose insulating layers is used in stable Li‐metal anodes. The conductivity gradient system guides the nucleation sites of Li‐metal to be directed during electrochemical plating. Additionally, the controlled parameter of the intermediate layer affects the highly stable Li‐metal plating. The electrochemical behavior is confirmed through experiments associated with the COMSOL Multiphysics simulation data. The distributed Li‐ion reaction flux resulting from the controlled electrical conductivity enables stable cycling for more than 250 cycles at 1 mA cm−2. The gradient system effectively suppresses dendrite growth even at a high current density of 5 mA cm−2 and ensures Li plating and stripping with ultra‐long‐term stability. To demonstrate the high‐energy‐density full‐cell application of the developed anode, it is paired with the LiNi0.8Co0.1Mn0.1O2 cathode. The cells demonstrate a high capacity retention of 90% with an extremely high Coulombic efficiency of 99.8% over 100 cycles. These results shed light on the formidable challenges involved in exploiting the engineering aspects of high‐energy‐density Li‐metal batteries.
An electrical conductivity gradient interfacial host composed of simply fabricated 1D high conductivity copper nanowires and nanocellulose insulating layers shows stable lithium metal plating/stripping during electrochemical reaction. The conductivity gradient offers to guide the nucleation of lithium metal deposition, resulting in a high capacity retention of 90% with an extremely high Coulombic efficiency of 99.8% over 100 cycles as a full‐cell test.
Background: Descriptive epidemiologists have repeatedly reported that males are more susceptible to head and neck cancers. However, most published data are those of cross-sectional studies, and no ...population-based cohort study has yet been published. The aim of this study was to compare the prevalence of head and neck cancers in healthy males with females. Methods: A retrospective cohort study using the Korean National Health Insurance Service database on 9,598,085 individuals who underwent regular health checkups from 1 January to 31 December 2009. We sought head and neck cancers developed during the 10-year follow-up. Results: A total of 10,732 (incidence rate (IR) per 1000 person-years 0.25) individuals were newly diagnosed with head and neck cancer among the 9,598,085 individuals during the 10-year follow-up. The IR was 0.19 in males (8500 affected) and 0.06 in females (2232 affected). Notably, the male−female ratio increased with age below 70 years but decreased thereafter. The male−female difference was most apparent for laryngeal cancer; the male IR was 11-fold higher in the 40 s and 20-fold higher in the 60 s, followed by hypopharyngeal cancer (6.8- and 24.2-fold). Males smoked more and drank more alcohol than females (p < 0.0001 *, p < 0.0001 *). When never-smokers/-drinkers (only) were compared, males remained at a 2.9-fold higher risk of head and neck cancer than females. The hazard ratios for head and neck cancers in males tended to increase in the lower part of the upper aerodigestive tract: larynx (13.9) > hypopharynx (10.9) > oropharynx (4.4) > nasopharynx (2.9) > sinonasal region (1.8) > oral (1.6). Only the salivary gland cancer incidence did not differ between the sexes; the gland is not in the upper aerodigestive tract. Conclusion: Males are much more susceptible to head and neck cancers than females regardless of whether they drink alcohol or smoke tobacco. Sex differences in the incidence of head and neck cancer are most evident in the 60 s in the lower part of the upper aerodigestive tract, such as the larynx and hypopharynx.
A facile, scalable route to new nanocomposites that are based on carbon nanotubes/heteroatom‐doped carbon (CNT/HDC) core–sheath nanostructures is reported. These nanostructures were prepared by the ...adsorption of heteroatom‐containing ionic liquids on the walls of CNTs, followed by carbonization. The design of the CNT/HDC composite allows for combining the electrical conductivity of the CNTs with the catalytic activity of the heteroatom‐containing HDC sheath layers. The CNT/HDC nanostructures are highly active electrocatalysts for the oxygen reduction reaction and displayed one of the best performances among heteroatom‐doped nanocarbon catalysts in terms of half‐wave potential and kinetic current density. The four‐electron selectivity and the exchange current density of the CNT/HDC nanostructures are comparable with those of a Pt/C catalyst, and the CNT/HDC composites were superior to Pt/C in terms of long‐term durability and poison tolerance. Furthermore, an alkaline fuel cell that employs a CNT/HDC nanostructure as the cathode catalyst shows very high current and power densities, which sheds light on the practical applicability of these new nanocomposites.
A facile, scalable route for the synthesis of new nanocomposites that are based on carbon nanotubes/heteroatom‐doped carbon (CNT/HDC) core–sheath nanostructures has been developed. The CNT/HDC nanostructures exhibit excellent electrocatalytic activity, kinetics, and durability for the oxygen reduction reaction, and they also performed well as the cathode catalysts in alkaline fuel cells.
Developing highly active and stable cathode catalysts is of pivotal importance for proton exchange membrane fuel cells (PEMFCs). While carbon‐supported nanostructured Pt‐based catalysts have so far ...been the most active cathode catalysts, their durability and single‐cell performance are yet to be improved. Herein, self‐supported mesostructured Pt‐based bimetallic (Meso‐PtM; M = Ni, Fe, Co, Cu) nanospheres containing an intermetallic phase are reported, which can combine the beneficial effects of transition metals (M), an intermetallic phase, a 3D interconnected framework, and a mesoporous structure. Meso‐PtM nanospheres show enhanced oxygen reduction reaction (ORR) activity, compared to Pt black and Pt/C catalysts. Notably, Meso‐PtNi containing an intermetallic phase exhibits ultrahigh stability, showing enhanced ORR activity even after 50 000 potential cycles, whereas Pt black and Pt/C undergo dramatic degradation. Importantly, Meso‐PtNi with an intermetallic phase also demonstrated superior activity and durability when used in a PEMFC single‐cell, with record‐high initial mass and specific activities.
Self‐supported mesostructured PtM (Meso‐PtM) nanospheres containing an intermetallic phase have been prepared, which show enhanced oxygen reduction reaction (ORR) activity compared to Pt/C and Pt black catalysts. Meso‐PtNi containing an intermetallic phase exhibits ultrahigh stability, showing enhanced ORR activity even after 50 000 potential cycles. In a proton exchange membrane fuel cell single‐cell test, Meso‐PtNi with intermetallic phase demonstrates record‐high initial performances and very high durability.
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