Improving vanadium removal from contaminated river water in constructed wetlands: The role of arbuscular mycorrhizal fungi.

Industrial activities pose a significant ecological risk to water resources as they pollute surrounding waters with vanadium (V). Although the contribution of plants and substrates to V removal in constructed wetlands (CWs) has been reported, the role of arbuscular mycorrhizal fungi (AMF) is unclear. The aim of the present study was to investigate the role of AMF in V removal in CWs and to elucidate the underlying mechanisms. Reed plants (Phragmites australis) were inoculated with an AMF strain (Rhizophagus irregularis) in CW columns, creating AMF-inoculated (+AMF) and non-inoculated (-AMF) treatments. Three levels of influent V concentrations (low: 0.50 mg L-1, medium: 1.14 mg L-1 and high: 1.52 mg L-1) were examined. The + AMF treatment showed higher V removal (60%-98%) than the control (40%-82%) in all three conditions, although the difference was not significant in some cases. The mean mycorrhizal effects were 75%, 19%, and 28% for low, moderate, and high influent V concentrations, respectively. The +AMF treatment showed a higher GRSP-bonded V concentration (5.5 mg g-1) than the -AMF treatment (4.0 mg g-1). Furthermore, +AMF treatment showed larger plants with higher V concentrations in their tissues, accompanied by increased biological concentration factors and biological accumulation factors. Given the remarkable positive effect of AMF on V removal, our study suggests that treating AMF in CWs is a worthwhile approach.

Toxic effects of aging mask microplastics on E. coli and dynamic changes in extracellular polymeric matter.

Contamination of disposable medical masks has become a growing problem globally in the wake of Covid-19 due to their widespread use and improper disposal. Three different mask layers, namely the outer layer, the meltblown (MB) filler layer and the inner layers release three different types of microplastics, whose physical and chemical properties change after prolonged environmental weathering. In this study, physical and chemical changes of mask microplastics before and after aging were characterized by different characterization techniques. The toxic effect and mechanism of aged mask microplastics on Escherichia coli (E. coli) were studied by measuring the growth inhibition of mask microplastics, the change in ATPase activity, the change in malondialdehyde content and reactive oxygen species production, and the release of the chemical composition of exopolymeric substances (EPS). The microplastics of the aged MB filter layer had the most significant inhibitory effect on E. coli growth, reaching 19.2 % after 36 h. Also, under the influence of mask microplastics, ATPase activity of E. coli was inhibited and a large amount of EPS was released. The chemical composition of EPS has also changed. This study proposed the possible toxicity mechanism of mask microplastics and the self-protection mechanism of E. coli, and provided a reference for future research on the toxic effects of mask microplastics on environmental organisms.

One-step hydrothermal generation of oxygen-deficient N-doped blue TiO2-Ti3C2 for degradation of pollutants and antibacterial properties.

In this study, TiO2 was generated in situ on the surface of Ti3C2 by a hydrothermal process, and urea was added to form N-doped TiO2-Ti3C2. The surface morphology and functional group properties of the prepared materials were analyzed by SEM, TEM, XRD, XPS, etc. The results showed that anatase TiO2 formed on the surface of the Ti3C2 monolayer. Nitrogen-doped nanomaterials show good phenol degradation and good recyclability under visible light. At a urea content of 0.5 g, the photocatalytic degradation of phenol under visible light is best, reaching 88.9% in 3 h, with ·OH and ·O2- holes playing the leading role. However, at lower pH and higher ion concentration, the degradability of N-TiO2-Ti3C2 for phenol is reduced. Furthermore, the material prepared in this work is a two-dimensional layered material, and the adsorption of phenol best fits the Langmuir adsorption isotherm model and the pseudo-second-order kinetic equation. In terms of the antibacterial performance of the material, the N-doped TiO2-Ti3C2 nanomaterial made with 0.2 g of urea has an Escherichia coli scavenging efficiency of about 97.86%, which is an excellent antibacterial material. This study shows that the N-TiO2-Ti3C2 produced in this experiment can be used for environmental applications.

Different weathering conditions affect the release of microplastics by masks.

A generation of microplastics caused by improper disposal of disposable masks has become a non-negligible environmental concern. In order to investigate the degradation mechanisms of masks and the release of microplastics under different environmental conditions, the masks are placed in 4 common environments. After 30 days of weathering, the total amount and release kinetics of microplastics released from different layers of the mask were studied. The chemical and mechanical properties of the mask were also discussed. The results showed that the mask released 25141±3543 particles/mask into the soil, which is much more than the sea and river water. The release kinetics of microplastics fit the Elovich model better. All samples correspond to the release rate of microplastics from fast to slow. Experiments show that the middle layer of the mask is released more than the other layers, and the amount of release was highest in the soil. And the tensile capacity of the mask is negatively correlated with its ability to release microplastics in the following order, which are soil > seawater > river > air > new masks. In addition, during the weathering process, the C-C/C-H bond of the mask was broken.

A Fast Finite-Time Neural Network Control of Stochastic Nonlinear Systems.

This article takes a fast finite-time control of stochastic nonlinear systems into account. The presence of unknown stochastic disturbance terms makes the traditional fast finite-time control approaches unavailable. To deal with this difficulty, by establishing an auxiliary function and using Jensen's inequality, in Lemma 6, a new criterion of fast finite-time stability is first established for the uncertain stochastic system. Based on the approximation ability of neural networks (NNs), an innovative fast finite-time strategy is put forward for stochastic nonlinear systems. Furthermore, by adopting the presented fast finite-time stability criterion, the stability of the stochastic systems is confirmed. Finally, two simulations are implemented to validate the feasibility of the presented NN control strategy.

Exploring the toxicity of the aged styrene-butadiene rubber microplastics to petroleum hydrocarbon-degrading bacteria under compound pollution system.

As a new pollutant, microplastics have increasingly drawn public attention to its toxic behavior in the environment. The aim was to investigate the effect of styrene-butadiene-rubber microplastics (mSBR) with different degrees of aging on petroleum hydrocarbon (PHC) degrading bacteria in an environment with simultaneously existing pollutants. A series of experiments were carried out to investigate the changes in the physical and chemical properties of mSBR with aging and to examine the influence of these changes on the inhibition of PHC-degrading bacteria by mSBR in the vicinity of coexisting pollutants. The results showed that in the early stage of ultraviolet aging (10d), the particle surface shows wrinkles, but the structure is intact. After reaching the late stage of aging (20d), nano-scale fragments were generated on the surface of mSBR, the average particle size decreased from 3.074 µm to 2.297 µm, and the zeta potential increased from - 25.1 mV to - 33.1 mV. The inhibitory effect of bacteria is greater. At the same time, these changes in the physicochemical properties increase the adsorption effect of Cd by 20%, and also improve the stability of mSBR in solution, whereby bacterial growth is inhibited by inhibiting the LPO activity and protein concentration of PHC degrading bacteria.

Application of PAFC/CPAM for the removal of ZnO nanoparticles by enhanced coagulation.

To cope with the increasingly severe challenges of zinc oxide nanoparticles (ZnO-NPs) in the field of the aquatic environment, this paper uses poly-aluminum ferric chloride (PAFC) and cationic polyacrylamide (CPAM) as coagulants to enhance the removal of ZnO-NPs from water. In two environments (pure-water environment and kaolin environment) that simulate suspended solids, we studied the dosage, pH, precipitation time, and hydraulic power of ZnO-NPs at three different initial concentrations (1, 2, and 30 mg/L). The effects of various conditions on the performance of PAFC, CPAM, and PAFC/CPAM to remove ZnO-NPs were examined. Results showed that the overall removal rate of ZnO-NPs in the kaolin environment was slightly higher than that in the pure-water environment. In contrast the removal rate of ZnO-NPs in the PAFC/CPAM was significantly higher than that of PAFC or CPAM alone. The coagulation removal conditions of ZnO-NPs were optimized using a response-surface model. Under the best conditions, the removal rate of ZnO-NPs with an initial mass concentration of 30 mg/L in the PAFC/CPAM combination in pure-water and kaolin environments was 98.54% and 99.17%, respectively. Finally, by studying the changes in floc size during coagulation, enhanced coagulation was an efficient method of removing ZnO-NPs from water.

Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors.

BACKGROUND: Despite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence of multifocal/disseminated disease in patients increases their mortality risk. Hence, the development of novel strategies to effectively treat patients with melanomas that are resistant to anti-PD1 mAb (αPD1) and/or Brafi, particularly those with multifocal/disseminated disease remains a major unmet clinical need. METHODS: Mice developing induced/spontaneous BrafV600E/Pten-/- melanomas were treated by cutaneous immunization with a DNA vaccine encoding the melanoma-associated antigen TRP2, with Brafi or αPD1 alone, or with a combination of these treatments. Tumor progression, tumor-infiltration by CD4+ and CD8+ T cells, and the development of TRP2-specific CD8+ T cells were then monitored over time. RESULTS: Vaccination led to durable antitumor immunity against PD1/Brafi-resistant melanomas in both single lesion and multifocal disease models, and it sensitized PD1-resistant melanomas to salvage therapy with αPD1. The therapeutic efficacy of the vaccine was associated with host skin-resident cells, the induction of a systemic, broadly reactive IFNγ+CD8+ T cell repertoire, increased frequencies of CD8+ TIL and reduced levels of PD1hi/intCD8+ T cells. Extended survival was associated with improved TIL functionality, exemplified by the presence of enhanced levels of IFNγ+CD8+ TIL and IL2+CD4+ TIL. CONCLUSIONS: These data support the use of a novel genetic vaccine for the effective treatment of localized or multifocal melanoma refractory to conventional αPD1-based and/or Brafi-based (immune)therapy.

Suitability of Mycorrhiza-Defective Rice and Its Progenitor for Studies on the Control of Nitrogen Loss in Paddy Fields via Arbuscular Mycorrhiza.

Employing mycorrhiza-defective mutants and their progenitors does not require inoculation or elimination of the resident microbial community in the experimental study of mycorrhizal soil ecology. We aimed to examine the suitability of mycorrhiza-defective rice (non-mycorrhizal, Oryza sativa L., cv. Nipponbare) and its progenitor (mycorrhizal) to evaluate nitrogen (N) loss control from paddy fields via arbuscular mycorrhizal (AM) fungi. We grew the two rice lines in soils with the full community of AM fungi and investigated root AM colonization. In the absence of AM fungi, we estimated rice N content, soil N concentration and microbial community on the basis of phospholipid fatty acids; we also quantified N loss via NH3 volatilization, N2O emission, runoff and leaching. In the presence of AM fungi, we did not find any evidence of AM colonization for non-mycorrhizal rice while mycorrhizal rice was colonized and percentage of root colonization was 17-24%. In the absence of AM fungi, the two rice lines had similar N content, soil N concentration and microbial community. Importantly, there was no significant difference in N loss via all the four pathways between mycorrhizal and non-mycorrhizal systems. This mycorrhizal/non-mycorrhizal rice pair is suitable for further research on the role of AM fungi in the control of soil N loss in paddy fields.

Red soil amelioration and heavy metal immobilization by a multi-element mineral amendment: Performance and mechanisms.

This field study aims to identify the performance and mechanisms of red soil amelioration and heavy metal immobilization by a multi-element mineral amendment (MMA) mainly containing a mixture of zeolites (laumontite and gismondine), montmorillonite, gehlenite, grossular and calcium silicate powder. The results indicated that the acidity of red soil was neutralized, and the soil EC, CEC, and content of montmorillonite and illite were increased after application of MMA, improving the soil fertility as well as the ability of heavy metals immobilization. The high amounts and reactivity of dissolved and colloidal Fe provided by the ferralsol (red soil) combined with the abundant available Si, Ca, Mg, Na and K supplied by MMA, readily destabilizes kaolinite and facilitates the formation of 2:1 type clay minerals. Meanwhile, the application of MMA was effective in reducing the bioavailability of soil heavy metals due to the activated mineralogical compositions of MMA as well as the increase of pH and 2:1 type clay minerals in the soil, which significantly decreased the up-taking and accumulation of Cd, Pb, Cr and Hg in lettuce tissues (p < 0.05). Compared with the untreated soil, the plant height, the total yield and content of vitamin C in the edible parts of lettuce in MMA-treated soil was increased by 7.6%, 23.6%, and 12.8%, respectively. These results showed that MMA could be a promising amendment for red soil amelioration and heavy metal immobilization.

Performance evaluation of modified bioretention systems with alkaline solid wastes for enhanced nutrient removal from stormwater runoff.

Bioretention systems have been found to be potential candidates for the removal of various pollutants/nutrients from rainfall or stormwater runoff. Despite bioretention has been widely developed for the removal of nutrients from stormwater, effective removal of both phosphorus and nitrogen is still a challenge. Hence, in this study, bioretention systems modified by alkaline solid waste media have been reported for the effective removal of nutrients. Six different types of solid wastes were first assessed using leaching and adsorption tests, and then the bottom ash from a refuse incineration plant was selected as a modifier. The bottom ash was mixed with soil to form a special media as the filter layer in the bioretention systems. The nutrient removal efficiencies of the modified bioretention systems were evaluated and also compared with those of the unmodified control. For this purpose, the design of the modified filter media with a saturated zone was combined to enhance the simultaneous removal of nitrogen and phosphorus. The effect of different rainfall intensities and nutrient concentrations in stormwater runoff on the removal efficiency of nutrients was evaluated. The results indicated that the modified bioretention with bottom ash modified soil media and saturated zone could exhibit the excellent removal efficiency of nitrogen and phosphorus from stormwater runoff. The extent of removal of total nitrogen, total Kjeldahl nitrogen, and total phosphorus was found to be 58-70%, 66-82% and 82-97%, respectively. The performed correlation analysis showed that the bioretention cell using the special media could simultaneously enhance the removal of phosphorus and nitrogen. As a part of this study, the adsorption isotherms of phosphorus removal by the modified bioretention systems have also been determined. Finally, the implications and opportunities for deploying modified bioretention systems for optimizing water-energy nexus and stormwater management were illustrated. In overall, this study demonstrated that the modified bioretention systems could substantially enhance the removal efficiencies of nutrients from stormwater runoff.

Melanoma-Induced Reprogramming of Schwann Cell Signaling Aids Tumor Growth.

The tumor microenvironment has been compared with a nonhealing wound involving a complex interaction between multiple cell types. Schwann cells, the key regulators of peripheral nerve repair, have recently been shown to directly affect nonneural wound healing. Their role in cancer progression, however, has been largely limited to neuropathic pain and perineural invasion. In this study, we showed that melanoma activated otherwise dormant functions of Schwann cells aimed at nerve regeneration and wound healing. Such reprogramming of Schwann cells into repair-like cells occurred during the destruction and displacement of neurons as the tumor expanded and via direct signaling from melanoma cells to Schwann cells, resulting in activation of the nerve injury response. Melanoma-activated Schwann cells significantly altered the microenvironment through their modulation of the immune system and the extracellular matrix in a way that promoted melanoma growth in vitro and in vivo. Local inhibition of Schwann cell activity following cutaneous sensory nerve transection in melanoma orthotopic models significantly decreased the rate of tumor growth. Tumor-associated Schwann cells, therefore, can have a significant protumorigenic effect and may present a novel target for cancer therapy. SIGNIFICANCE: These findings reveal a role of the nerve injury response, particularly through functions of activated Schwann cells, in promoting melanoma growth.

Arbuscular mycorrhizal fungi increase grain yields: a meta-analysis.

Increasing grain yields of food cereal crops is a major goal in future sustainable agriculture. We quantitatively analyzed the potential role of arbuscular mycorrhizal (AM) fungi in enhancing grain yields of seven cereal crops with exceptional importance for human nutrition across the globe: corn, wheat, rice, barley, sorghum, millet and oat. We conducted a meta-analysis for three datasets including both English and Chinese language publications: the 'whole' dataset including both laboratory and field studies (168 articles); the 'field' dataset comprising only field studies (97 studies); and the 'field-inoculation' dataset including only AM fungal inoculation studies conducted in field conditions (70 articles). We found that the AM fungal effect on grain yield was less pronounced in field and noninoculation studies. AM fungal inoculation in field led to a 16% increase (overall effect) based on the 'field-inoculation' dataset; this effect was variable (77% trials had positive values), crop-specific, lower for new cultivars released after 1950 and further modulated by soil pH. Although there are neutral and negative effects of AM fungi on grain yields, we emphasize the importance of integrating AM fungi in sustainable agriculture to increase grain yields of cereal crops.

Effective treatment of emulsified oil wastewater by the coagulation-flotation process.

Ship emulsified oil wastewater was used as the research object in this study. The highly efficient coagulant demulsification degreasing mechanism and microbubble flotation technology were combined and the effects of coagulant type and dosage amount on the demulsification of emulsified oil wastewater were evaluated. The influence of the mixed coagulation effect of pH values, temperature, and hydraulic condition parameters were determined and water intake, air intake, and oil content were regulated. The coagulant for the demulsification of emulsified oil wastewater was screened; the dosage was 500 mg L-1, and the removal capacity of the coagulant was in the following order: polyaluminum ferric chloride (PAFC) > polyaluminum chloride (PAC) > polysilicate aluminum ferric sulfate (PSAFS) > alum > Al2(SO4)3 > polyferric sulfate > FeCl3. Polyacrylamide (PAM) with added water was used to further reduce the oil content. The PAFC, PAC, and PSAFS were selected as coagulation-air flotation dynamic test alternative agents. The investment quantities of PAFC, PSAFS and PAM were 300 mg L-1, 300 mg L-1 and 30 mg L-1, respectively. The stirring time was 5 min, the pH value was 6.5-6.9, the flow rate was 0.25 m3 h-1, the oil content of the emulsified oil wastewater was 3000-5000 mg L-1 and the effluent oil was stable below 15 ppm. The microbubble generation device using air flotation effluent was used in the two air flotation treatments to enhance the device efficiency. The air flotation device adopted the structural design of the upper part of the water inlet and the lower part of the micro-air bubble, which can increase the collision probability of the microbubble and improve the efficiency of oil removal.

Tumor-derived high-mobility group box 1 and thymic stromal lymphopoietin are involved in modulating dendritic cells to activate T regulatory cells in a mouse model.

High-mobility group box 1 (HMGB1) is involved in the tumor-associated activation of regulatory T cells (Treg), but the mechanisms remain unknown. In a mouse tumor model, silencing HMGB1 in tumor cells or inhibiting tumor-derived HMGB1 not only dampened the capacity of tumor cells to produce thymic stromal lymphopoietin (TSLP), but also aborted the tumor-associated modulation of Treg-activating DC. Tumor-derived HMGB1 triggered the production of TSLP by tumor cells. Importantly, both tumor-derived HMGB1 and TSLP were necessary for modulating DC to activate Treg in a TSLP receptor (TSLPR)-dependent manner. In the therapeutic model, intratumorally inhibiting tumor-derived HMGB1 (causing downstream loss of TSLP production) attenuated Treg activation, unleashed tumor-specific CD8 T cell responses, and elicited CD8α+/CD103+DC- and T cell-dependent antitumor activity. These results suggest a new pathway for the activation of Treg involving in tumor-derived HMGB1 and TSLP, and have important implications for incorporating HMGB1 inhibitors into cancer immunotherapy.

Intratumoral delivery of tumor antigen-loaded DC and tumor-primed CD4+ T cells combined with agonist α-GITR mAb promotes durable CD8+ T-cell-dependent antitumor immunity.

The progressive tumor microenvironment (TME) coordinately supports tumor cell expansion and metastasis, while it antagonizes the survival and (poly-)functionality of antitumor T effector cells. There remains a clear need to develop novel therapeutic strategies that can transform the TME into a pro-inflammatory niche that recruits and sustains protective immune cell populations. While intravenous treatment with tumor-primed CD4+ T cells combined with intraperitoneal delivery of agonist anti-glucocorticoid-induced TNF receptor (α-GITR) mAb results in objective antitumor responses in murine early stage disease models, this approach is ineffective against more advanced tumors. Further subcutaneous co-administration of a vaccine consisting of tumor antigen-loaded dendritic cells (DC) failed to improve the antitumor efficacy of this approach. Remarkably, these same three therapeutic agents elicited significant antitumor benefits when the antitumor CD4+ T cells and tumor antigen-loaded DC were co-injected directly into tumors along with intratumoral or intraperitoneal delivery of α-GITR mAb. This latter protocol induced the production of an array of antitumor cytokines and chemokines within the TME, supporting increased tumor-infiltration by antitumor CD8+ T cells capable of mediating tumor regression and extended overall survival.

Genetic vaccines to potentiate the effective CD103+ dendritic cell-mediated cross-priming of antitumor immunity.

The development of effective cancer vaccines remains an urgent, but as yet unmet, clinical need. This deficiency is in part due to an incomplete understanding of how to best invoke dendritic cells (DC) that are crucial for the induction of tumor-specific CD8(+) T cells capable of mediating durable protective immunity. In this regard, elevated expression of the transcription factor X box-binding protein 1 (XBP1) in DC appears to play a decisive role in promoting the ability of DC to cross-present Ags to CD8(+) T cells in the therapeutic setting. Delivery of DNA vaccines encoding XBP1 and tumor Ag to skin DC resulted in increased IFN-α production by plasmacytoid DC (pDC) from skin/tumor draining lymph nodes and the cross-priming of Ag-specific CD8(+) T cell responses associated with therapeutic benefit. Antitumor protection was dependent on cross-presenting Batf3(+) DC, pDC, and CD8(+) T cells. CD103(+) DC from the skin/tumor draining lymph nodes of the immunized mice appeared responsible for activation of Ag-specific naive CD8(+) T cells, but were dependent on pDC for optimal effectiveness. Similarly, human XBP1 improved the capacity of human blood- and skin-derived DC to activate human T cells. These data support an important intrinsic role for XBP1 in DC for effective cross-priming and orchestration of Batf3(+) DC-pDC interactions, thereby enabling effective vaccine induction of protective antitumor immunity.

Dendritic cell-derived interleukin-15 is crucial for therapeutic cancer vaccine potency.

IL-15 supports improved antitumor immunity. How to best incorporate IL-15 into vaccine formulations for superior cancer immunotherapy remains a challenge. DC-derived IL-15 (DCIL-15) notably has the capacity to activate DC, to substitute for CD4+ Th and to potentiate vaccine efficacy making IL-15-based therapies attractive treatment options. We observed in transplantable melanoma, glioma and metastatic breast carcinoma models that DCIL-15-based DNA vaccines in which DC specifically express IL-15 and simultaneously produce tumor Aghsp70 were able to mediate potent therapeutic efficacy that required both host Batf3+ DC and CD8+ T cells. In an inducible BrafV600E/Pten-driven murine melanoma model, DCIL-15 (not rIL-15)-based DNA vaccines elicited durable therapeutic CD8+ T cell-dependent antitumor immunity. DCIL-15 was found to be superior to rIL-15 in "licensing" both mouse and human DC, and for activating CD8+ T cells. Such activation occurred even in the presence of Treg, without a need for CD4+ Th, but was IL-15/IL-15Rα-dependent. A single low-dose of DCIL-15 (not rIL-15)-based DC vaccines induced therapeutic antitumor immunity. CD14+ DC emigrating from human skin explants genetically-immunized by IL-15 and Aghsp70 were more effective than similar DC emigrating from the explants genetically-immunized by Aghsp70 in the presence of rIL-15 in expressing membrane-bound IL-15/IL-15Rα and activating CD8+ T cells. These results support future clinical use of DCIL-15 as a therapeutic agent in battling cancer.

Genetic targeting of the active transcription factor XBP1s to dendritic cells potentiates vaccine-induced prophylactic and therapeutic antitumor immunity.

In vivo dendritic cells (DC) targeting is an attractive approach with potential advantages in vaccine efficacy, cost, and availability. Identification of molecular adjuvants to in vivo "modulate " DC to coordinately render improved Th1 and CD8 T cell immunity, and attenuated deleterious Treg effects, is a critical challenge. Here, we report that in vivo genetic targeting of the active transcription factor XBP1s to DC (XBP1s/DC) potentiated vaccine-induced prophylactic and therapeutic antitumor immunity in multiple tumor models. This immunization strategy is based on a genetic vaccine encoding both cytomegalovirus (CMV)-driven vaccine Aghsp70 and DC-specific CD11c-driven XBP1s. The novel targeted vaccine induced durable Th1 and CD8 T cell responses to poorly immunogenic self/tumor antigen (Ag) and attenuated tumor-associated Treg suppressive function. Bone marrow (BM)-derived DC genetically modified to simultaneously overexpress XBP1s and express Aghsp70 upregulated CD40, CD70, CD86, interleukin (IL)-15, IL-15Rα, and CCR7 expression, and increased IL-6, IL-12, and tumor necrosis factor (TNF)-α production in vitro. XBP1s/DC elevated functional DEC205(+)CD8α(+)DC in the draining lymph nodes (DLN). The data suggest a novel role for XBP1s in modulating DC to potentiate tumor vaccine efficacy via overcoming two major obstacles to tumor vaccines (i.e., T cell hyporesponsiveness against poorly immunologic self/tumor Ag and tumor-associated Treg-mediated suppression) and improving DEC205(+)CD8α(+)DC.

Knockdown of HMGB1 in tumor cells attenuates their ability to induce regulatory T cells and uncovers naturally acquired CD8 T cell-dependent antitumor immunity.

Although high mobility group box 1 (HMGB1) in tumor cells is involved in many aspects of tumor progression, its role in tumor immune suppression remains elusive. Host cell-derived IL-10 suppressed a naturally acquired CD8 T cell-dependent antitumor response. The suppressive activity of tumor-associated Foxp3(+)CD4(+)CD25(+) regulatory T cells (Treg) was IL-10 dependent. Neutralizing HMGB1 impaired tumor cell-promoted IL-10 production by Treg. Short hairpin RNA-mediated knockdown of HMGB1 (HMGB1 KD) in tumor cells did not affect tumor cell growth but uncovered naturally acquired long-lasting tumor-specific IFN-γ- or TNF-α-producing CD8 T cell responses and attenuated their ability to induce Treg, leading to naturally acquired CD8 T cell- or IFN-γ-dependent tumor rejection. The data suggest that tumor cell-derived HMGB1 may suppress naturally acquired CD8 T cell-dependent antitumor immunity via enhancing Treg to produce IL-10, which is necessary for Treg-mediated immune suppression.