Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing.

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.

Bubbles in Porous Electrodes for Alkaline Water Electrolysis.

Porous electrodes with high specific surface areas have been commonly employed for alkaline water electrolysis. The gas bubbles generated in electrodes due to water electrolysis, however, can screen the reaction sites and hinder reactant transport, thereby deteriorating the performance of electrodes. Hence, an in-depth understanding of the behavior of bubbles in porous electrodes is of great importance. Nevertheless, since porous electrodes are opaque, direct observation of bubbles therein is still a challenge. In this work, we have successfully captured the behavior of bubbles in the pores at the side surfaces of nickel-based porous electrodes. Two types of porous electrodes are employed: the ones with straight pores along the gravitational direction and the ones with tortuous pores. In the porous electrodes with tortuous pores, the moving bubbles are prone to collide with the solid matrix, thereby leading to the accumulation of bubbles in the pores and hence bubble trapping. By contrast, in the porous electrodes with straight pores, bubbles are seldom trapped; and when two bubbles near the wall surfaces coalesce, the merged bubble can jump away from the wall surfaces, releasing more active surfaces for reaction. As a result, the porous electrodes with straight pores, although with lower specific surface areas, are superior to those with tortuous pores. The relationship among the pore structures of porous electrodes, bubble behavior, and electrode performance disclosed in this work provides deep insights into the design of porous electrodes.

Engineering Phase Transition from 2H to 1T in MoSe2 by W Cluster Doping toward Lithium-Ion Battery.

Phase engineering synthesis strategy is extremely challenging to achieve stable metallic phase molybdenum diselenide for a better physicochemical property than the thermodynamically stable semiconducting phase. Herein, we introduce tungsten atom clusters into the MoSe2 layered structure, realizing the phase transition from the 2H semiconductor to 1T metallic phase at a high temperature. The combination of synchrotron radiation X-ray absorption spectroscopy, Cs-corrected transmission electron microscopy, and theoretical calculation demonstrates that the aggregation doping of W atoms is the factor of MoSe2 structure transformation. When utilizing this distinct structure as an anode component, it demonstrates outstanding rate capability and durability. After 500 cycles, this results in a specific capacity of 1007.4 mAh g-1 at 500 mA g-1. These discoveries could open the door for the future development of high-performance anodes for ion battery applications.

microRNA-301b-3p from mesenchymal stem cells-derived extracellular vesicles inhibits TXNIP to promote multidrug resistance of gastric cancer cells.

OBJECTIVE: MicroRNAs (miRNAs) from mesenchymal stem cells (MSC)-derived extracellular vesicles (MSCs-EVs), including exosomes, are known to participate in different diseases. However, the function of miR-301b-3p from MSCs-EVs on the chemoresistance of gastric cancer (GC) cells remains poorly characterized. Thus, we aim to explore the role of MSCs-EVs-derived miR-301b-3p in multidrug resistance of GC cells. METHODS: Cisplatin (DDP)/vincristine (VCR)-resistant and sensitive GC clinical samples were harvested to detect expression of miR-301b-3p and thioredoxin interacting protein (TXNIP). MSCs were respectively transfected with miR-301b-3p oligonucleotides and/or TXNIP plasmids to extract the EVs, which were then co-cultured with multidrug-resistant GC cells. Then, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), IC50, proliferation, migration, and apoptosis of resistant GC cells were determined. The tumor growth was observed in nude mice. Targeting relationship between miR-301b-3p and TXNIP was confirmed. RESULTS: miR-301b-3p was upregulated, and TXNIP was downregulated in DDP/VCR-resistant GC tissues and cells. MSC-EVs induced drug resistance, proliferation, and migration and inhibited apoptosis of DDP/VCR-resistant GC cells in vitro, as well as facilitated tumor growth in vivo. Inhibition of miR-301b-3p or upregulation of TXNIP reversed the promoting effect of MSC-EVs on DDP/VCR resistant GC cells to DDP/VCR resistance and malignant behaviors. The effects of MSC-EVs carrying miR-301b-3p inhibition on DDP/VCR-resistant GC cells were reversed by TXNIP downregulation. TXNIP was confirmed as a target gene of miR-301b-3p. CONCLUSION: miR-301b-3p from MSCs-EVs inhibits TXNIP to promote multidrug resistance of GC cells, providing a novel insight for chemotherapy in GC.

Controlled synthesis of transition metal oxide multi-shell structures andin situstudy of the energy storage mechanism.

Multi-shell transition metal oxide hollow spheres show great potential for applications in energy storage because of their unique multilayered hollow structure with large specific surface area, short electron and charge transport paths, and structural stability. In this paper, the controlled synthesis of NiCo2O4, MnCo2O4, NiMn2O4multi-shell layer structures was achieved by using the solvothermal method. As the anode materials for Li-ion batteries, the three multi-shell structures maintained good stability after 650 long cycles in the cyclic charge/discharge test. Thein situtransmisssion electron microscope characterization combined with cyclic voltammetry tests demonstrated that the three anode materials NiCo2O4, MnCo2O4and NiMn2O4have similar charge/discharge transition mechanisms, and the multi-shell structure can effectively buffer the volume expansion and structural collapse during lithium embedding/delithiation to ensure the stability of the electrode structure and cycling performance. The research results can provide effective guidance for the synathesis and charging/discharging mechanism of multi-shell metal oxide lithium-ion battery anode materials.

Mn(OAc)2-promoted [3+2] cyclization of enaminone with isocyanoacetate: Rapid access to pyrrole-2-carboxylic ester derivatives with potent anticancer activity.

The practical and facile Mn(OAc)2-promoted [3+2] cycloaddition reaction of enaminones with isocyanoacetate was developed, that delivered a diversity of 3-aroyl pyrrole-2-carboxylic esters with broad substrates scope. The most of the newly synthesized compounds exhibit moderate antiproliferative activity against four cancer cells. Notably, compound 2n demonstrate the most potent activity with average IC50 values of 5.61 µM against four distinct cancer cell lines. Moreover, 2n exhibit favorable anti-migration activity and drug-like properties. The further investigation suggests that compound 2n possesses the ability to inhibit ERK5 activity and exhibits effective binding with the ERK5 protein, making it a promising candidate as a lead compound for a new class of ERK5 inhibitors discovery.

Short-term efficacy of additional laparoscopic-assisted radical gastrectomy after non-curative endoscopic submucosal dissection for early gastric cancer.

OBJECTIVE: To investigate short-term efficacy of direct laparoscopic-assisted radical gastrectomy (LAG) versus non-curative endoscopic submucosal dissection (ESD) plus additional LAG for early gastric cancer. MATERIALS AND METHODS: 286 patients were retrospectively assigned into two groups: direct LAG group (n = 255) and additional LAG (ESD plus LAG, n = 31) group. A 1:2 propensity score matching was performed to equalize relevant confounding factors between two groups for analysis. RESULTS: Ninety-three patients were successfully matched, including 62 in the direct LAG group and 31 in the additional LAG group. A significant (P = 0.013) difference existed in the drainage removal time between the additional LAG and direct LAG group (7 d vs. 6 d). Age, sex, tumor location and surgical approach were significantly (P < 0.05) associated with complications, with age ≥ 60 years (P = 0.002) and total gastrectomy (P = 0.011) as significant independent risk factors. A significant (P = 0.023) difference existed in the surgical time between the early and late groups (193.3 ± 37.6 min vs. 165.5 ± 25.1 min). CONCLUSION: Additional LAG (D1 + lymphadenectomy) after ESD may be safe and effective even though non-curative ESD may prolong the drainage removal time and increase the difficulty of surgery.

Spatial heterogeneity and source apportionment of soil metal(loid)s in an abandoned lead/zinc smelter.

Metal smelting have brought severe metal(loid)s contamination to the soil. Spatial distribution and pollution source analysis for soil metal(loid)s in an abandoned lead/zinc smelter were studied. The results showed that soil was contaminated heavily with metal(loid)s. The mean of lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg) and antimony (Sb) content in topsoil is 9.7, 8.2, 5.0, 2.3, and 1.2 times higher than the risk screening value for soil contamination of development land of China (GB36600-2018), respectively. Cd is mainly enriched in the 0-6 m depth of site soil while As and Pb mainly deposited in the 0-4 m layer. The spatial distribution of soil metal(loid)s is significantly correlated with the pollution source in the different functional areas of smelter. As, Hg, Sb, Pb and copper (Cu) were mainly distributed in pyrometallurgical area, while Cd, thallium (Tl) and zinc (Zn) was mainly existed in both hydrometallurgical area and raw material storage area. Soil metal(loid)s pollution sources in the abandoned smelter are mainly contributed to the anthropogenic sources, accounting for 84.5%. Specifically, Pb, Tl, As, Hg, Sb and Cu mainly from atmospheric deposition (55.9%), Cd and Zn mainly from surface runoff (28.6%), While nickel (Ni) mainly comes from parent material (15.5%). The results clarified the spatial distribution and their sources in different functional areas of the smelter, providing a new thought for the risk prevention and control of metal(loid)s in polluted site soil.

Risk probability and influencing factors of stroke in followed-up hypertension patients.

OBJECTIVE: To explore the risk probability and main influencing factors of stroke in followed-up hypertension patients through the analysis of long-term followed-up cohort data. METHODS: The method of followed-up observation cohort was used to collect the information of 168,417 followed-up hypertension patients from 2002 to 2020 in Jiading District in Shanghai. Kaplan-Meier method was used to analyze the risk probability of stroke complications in long-term followed-up HTN patients, and the influencing factors were analyzed by Cox proportional risk model. RESULTS: Among 168,417 followed-up hypertension patients, 11,143 cases had suffered stroke, and the cumulative incidence rate of stroke was 6.62% (male was 6.87%, female was 6.37%). With the extension of the hypertension years, the cumulative risk probability of stroke in HTN patients would continue to increase and the interval was not equidistant. The total cumulative risk probability of stroke in HTN patients was 78.9% (male was 91.0%, female was 70.7%). During the period of hypertension, the risk occurring probability of stroke was not fixed, but fluctuating. There were 4 onset peaks, which were in 8 years (probability was 4.2%), 15 years (probability was 14.0%), 22 years (probability was 6.0%) and 26 years (probability was 13.9%). The highest risk probability of male patients was in 26 years (probability was 23.1%), and the second peak was in 15 years (probability was 15.6%). The highest risk probability of female patients was in 15 years (probability was 12.9%), and the second peak was in 26 years (probability was 8.7%). The risk probability of different gender, BP grade and BMI was different, the male were at higher risk than the female, stage 3 HTN was higher than stage 2 and stage 1 HTN, obese people and underweight people were at higher risk than those who have normal weight. The main factors closely related to the occurrence of stroke complications were age (RR = 2.917, p < 0.001), body mass index (RR = 1.654, p < 0.001), family history of stroke (RR = 1.386, p < 0.001) and blood pressure grade (RR = 1.148, p < 0.001). CONCLUSION: The risk probability of stroke among hypertension patients was high in followed-up hypertension patients (total 78.9%, male 91.0%, female 70.7%), and would continue to increase disproportionately during period of hypertension (4 different onset peaks). With the persistence of hypertension, the risk probability of stroke would increase continuously. Multivariate Cox regression analysis showed that male patients, patients with HBP, abnormal BMI and positive family history were main factors closely related to the occurrence of stroke complications.

Molecular dynamics-guided receptor-dependent 4D-QSAR studies of HDACs inhibitors.

Histone deacetylases (HDACs) were highlighted as a novel category of anticancer targets. Several HDACs inhibitors were approved for therapeutic use in cancer treatment. Comparatively, receptor-dependent 4D-QSAR, LQTA-QSAR, is a new approach which generates conformational ensemble profiles of compounds by molecular dynamics simulations at binding site of enzyme. This work describes a receptor-dependent 4D-QSAR studies on hydroxamate-based HDACs inhibitors. The 4D-QSAR model was generated by multiple linear regression method of QSARINS. Leave-N-out cross-validation (LNO) and Y-randomization were performed to analysis of the independent test set and to verify the robustness of the model. Best 4D-QSAR model showed the following statistics: R2 = 0.8117, Q2LOO = 0.6881, Q2LNO = 0.6830, R2Pred = 0.884. The results may be used for further virtual screening and design for novel HDACs inhibitors. The receptor dependent 4D-QSAR model was developed for the hydroxamate derivatives as HDAC inhibitors by making use of molecular dynamics simulation to obtain conformational ensemble profile for each compound. The multiple linear regression method was used to generate 4D-QSAR model with the suitable predictive ability and the excellent statistical parameters.

Molecular ammonia sensing of PEDOT:PSS/nitrogen doped MXene Ti3C2Txcomposite film at room temperature.

The irrational NH3emission routinely poses a significant threat to human health and environmental protection even at low dose. In addition, high miniaturization and low power-consumption has been the critical requirements of Internet of Things. To meet these demands, it is greatly pressing to develop a novel gas sensor with the capability to detect trace NH3without external heating or light-irradiation elements. In this work, the organic conducting conjugated polymer PEDOT:PSS was combined with inorganic nitrogen-doped transition metal carbides and nitrides (N-MXene Ti3C2Tx) for chemiresistive NH3sensing at room temperature (20oC). By means of the organic-inorganicn-pheterojunctions via the synergistic effect, the results show that the composite film sensor with the optimal mass ratio of 1:0.5 between N-MXene and PEDOT:PSS components delivered favorable NH3sensing performance than individual N-MXene or PEDOT:PSS counterparts in terms of higher response and quicker response/recovery speeds under 20oC@36%RH air. Besides, decent repeatability, stability and selectivity were demonstrated. The incorporated N atoms served as excellent electron donors to promote the electron-transfer reactions and augment the sorption sites. Simultaneously, partial oxidation of MXene brought about some TiO2nanoparticles which acted as spacers to widen the interlayer spacing and probably suppress the MXene restacking during the film deposition, thus favoring the gas diffusion/penetration within the sensing layer and then a quick reaction kinetic. The modulation of consequent build-in field within the heterojunctions was responsible for the reversible NH3sensing. In addition, pre-adsorbed water molecules facilitated to establish a swift adsorption/desorption balance. The proposed strategy expanded the application range of MXene based composite materials and enrich the current sensing mechanisms of NH3gas sensors.

miR-125a-5p promotes gastric cancer growth and invasion by regulating the Hippo pathway.

OBJECTIVE: This study was carried out to explore the potential involvement of miR-125a-5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression. METHODS: In vitro transfection of miR-125a-5p mimics or inhibitors, qRT-PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR-125a-5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR-125a-5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT-PCR, and immunoblotting were performed to explore the role of miR-125a-5p in the epithelial-mesenchymal transition (EMT) and association among miR-125a-5p, EphA2, TAZ, and TEAD2 in GC cells. RESULTS: MiR-125a-5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR-125a-5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR-125a-5p reversed EMT in vitro. miR-125a-5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR-125a-5p was overexpressed in late-stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2. CONCLUSION: miR-125a-5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.

Sorption kinetics, isotherms and mechanisms of PFOS on soils with different physicochemical properties.

Perfluorooctane sulfonate (PFOS), an emerging contaminant, is environmentally persistent, bioaccumulative and toxic to human health and ecosystems. It has been widely detected in groundwater, surface water, soil and sediment. So far, very few research has reported on the PFOS sorption behaviors onto soils, one of the primary processes that influence its fate and transport in the subsurface. In this study, the sorption and desorption of PFOS onto six soils with different physicochemical properties were investigated. Kinetic and equilibrium studies of PFOS sorption onto six soils were carried out in batch experiment. The sorption kinetics of PFOS on the six soils demonstrated that PFOS sorption reached equilibrium within 48h, and the well-fitted pseudo-second-order kinetic model to experimental data suggested that chemisorption was involved in PFOS sorption on soils. The intraparticle diffusion model results indicated that both film diffusion and intraparticle diffusion were the rate-limiting steps for five of the six soil samples, while the intraparticle diffusion was the only limiting step in the PFOS sorption on the sixth soil. PFOS sorption isotherms can be described by the Freundlich model well for all six soils (R2=0.979-0.999). The correlation analysis between KF of PFOS and the physicochemical properties of the soils showed that a positive correlation between KF and Al2O3, SOC and Fe2O3. The FTIR data demonstrated hydrophobic interaction, ion exchange, surface complexing and hydrogen bonding might all play a role in the PFOS sorption onto soil samples. PFOS sorption onto soil minerals, especially iron oxide minerals, needs to be further explored in future.

Microbial production of fatty-acid-derived fuels and chemicals from plant biomass.

Increasing energy costs and environmental concerns have emphasized the need to produce sustainable renewable fuels and chemicals. Major efforts to this end are focused on the microbial production of high-energy fuels by cost-effective 'consolidated bioprocesses'. Fatty acids are composed of long alkyl chains and represent nature's 'petroleum', being a primary metabolite used by cells for both chemical and energy storage functions. These energy-rich molecules are today isolated from plant and animal oils for a diverse set of products ranging from fuels to oleochemicals. A more scalable, controllable and economic route to this important class of chemicals would be through the microbial conversion of renewable feedstocks, such as biomass-derived carbohydrates. Here we demonstrate the engineering of Escherichia coli to produce structurally tailored fatty esters (biodiesel), fatty alcohols, and waxes directly from simple sugars. Furthermore, we show engineering of the biodiesel-producing cells to express hemicellulases, a step towards producing these compounds directly from hemicellulose, a major component of plant-derived biomass.

Small molecules targeting selected histone methyltransferases (HMTs) for cancer treatment: Current progress and novel strategies.

Histone methyltransferases (HMTs) play a critical role in gene post-translational regulation and diverse physiological processes, and are implicated in a plethora of human diseases, especially cancer. Increasing evidences demonstrate that HMTs may serve as a potential therapeutic target for cancer treatment. Thus, the development of HMTs inhibitor have been pursued with steadily increasing interest over the past decade. However, the disadvantages such as insufficient clinical efficacy, moderate selectivity, and propensity for acquired resistance have hindered the development of conventional HMT inhibitors. New technologies and methods are imperative to enhance the anticancer activity of HMT inhibitors. In this review, we first review the structure and biological functions of the several essential HMTs, such as EZH2, G9a, PRMT5, and DOT1L. The internal relationship between these HMTs and cancer is also expounded. Next, we mainly focus on the latest progress in the development of HMT modulators encompassing dual-target inhibitors, targeted protein degraders and covalent inhibitors from perspectives such as rational design, pharmacodynamics, pharmacokinetics, and clinical status. Lastly, we also discuss the challenges and future directions for HMT-based drug discovery for cancer therapy.

The pyrexia channel remodels egg-laying of Liriomyza huidobrensis in response to temperature change.

BACKGROUND: The pea leafminer, Liriomyza huidobrensis, is one of the most important insect pests on vegetables and ornamentals. The survival and egg-laying behavior of leafminers are markedly affected by the environment temperature. However, the mechanisms underlying the relationship between egg-laying and temperature are still largely unknown. RESULTS: Here, we find that leafminers have evolved an adaptive strategy to overcome the stress from high or low temperature by regulating oviposition-punching plasticity. We further show that this oviposition-punching plasticity is mediated by the expression of pyx in the ovipositor when subjected to disadvantageous temperature. Specifically, down-regulation of pyx expression in leafminers under low temperature stress led to a significant decrease in the swing numbers of ovipositor and puncture area of the egg spot, and consequently the lower amount of egg-laying compared to leafminers at ambient temperature. Conversely, activation of pyx expression under high temperature stress increased the swing numbers and puncture area, still resulting in a reduction of egg-laying amount. CONCLUSION: Thereby, leafminers are able to coordinate pyx channel expression level and accordingly depress the oviposition. Our study uncovers a molecular mechanism underlying the adaptive strategy in insects that can avoid disadvantageous temperature for reproducing offspring. © 2024 Society of Chemical Industry.

Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer.

Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from pro-tumorigenic to anti-tumor phenotypes and enhance ICB efficacy in PCa. Integration of four PCa single-cell RNA-sequencing datasets defined pro-tumorigenic and anti-tumor CAFs, and RNA-seq, flow cytometry, and a PCa organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an anti-tumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

Macrophage-Derived Nanosponges Adsorb Cytokines and Modulate Macrophage Polarization for Renal Cell Carcinoma Immunotherapy.

Renal cell carcinoma (RCC) is a hot tumor infiltrated by large numbers of CD8+ T cells and is highly sensitive to immunotherapy. However, tumor-associated macrophages (TAMs), mainly M2 macrophages, tend to undermine the efficacy of immunotherapy and promote the progression of RCC. Here, macrophage-derived nanosponges are fabricated by M2 macrophage membrane-coated poly（lactic-co-glycolic acid）（PLGA）, which could chemotaxis to the CXC and CC chemokine subfamily-enriched RCC microenvironment via corresponding membrane chemokine receptors. Subsequently, the nanosponges act like cytokine decoys to adsorb and neutralize broad-spectrum immunosuppressive cytokines such as colony stimulating factor-1(CSF-1), transforming growth factor-ß（TGF-ß）, and Lnterleukin-10（IL-10）, thereby reversing the polarization of M2-TAMs toward the pro-inflammatory M1 phenotype, and enhancing the anti-tumor effect of CD8+ T cells. To further enhance the polarization reprogramming efficiency of TAMs, DSPE-PEG-M2pep is conjugated on the surface of macrophage-derived nanosponges for specific recognition of M2-TAMs, and the toll like receptors 7/8（TLR7/8） agonist, R848, is encapsulated in these nanosponges to induce M1 polarization, which result in significant efficacy against RCC. In addition, these nanosponges exhibit undetectable biotoxicity, making them suitable for clinical applications. In summary, a promising and facile strategy is provided for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases.