Key Role of Vegetation Cover in Alleviating Microplastic-Enhanced Carbon Emissions.

Microplastics (MPs) are considered to influence fundamental biogeochemical processes, but the effects of plant residue-MP interactions on soil carbon turnover in urban greenspaces are virtually unknown. Here, an 84-day incubation experiment was constructed using four types of single-vegetation-covered soils (6 years), showing that polystyrene MP (PSMP) pollution caused an unexpectedly large increase in soil CO2 emissions. The additional CO2 originating from highly bioavailable active dissolved organic matter molecules (<380 °C, predominantly polysaccharides) was converted from persistent carbon (380-650 °C, predominantly aromatic compounds) rather than PSMP derivatives. However, the priming effect of PSMP derivatives was weakened in plant-driven soils (resistivity: shrub > tree > grass). This can be explained from two perspectives: (1) Plant residue-driven humification processes reduced the percentage of bioavailable active dissolved organic matter derived from the priming effects of PSMPs. (2) Plant residues accelerated bacterial community succession (dominated by plant residue types) but slowed fungal community demise (retained carbon turnover-related functional taxa), enabling specific enrichment of glycolysis, the citric acid cycle and the pentose phosphate pathway. These results provide a necessary theoretical basis to understand the role of plant residues in reducing PSMP harm at the ecological level and refresh knowledge about the importance of biodiversity for ecosystem stability.

Interactions among microorganisms functionally active for electron transfer and pollutant degradation in natural environments.

Compared to single microbial strains, complex interactions between microbial consortia composed of various microorganisms have been shown to be effective in expanding ecological functions and accomplishing biological processes. Electroactive microorganisms (EMs) and degradable microorganisms (DMs) play vital roles in bioenergy production and the degradation of organic pollutants hazardous to human health. These microorganisms can strongly interact with other microorganisms and promote metabolic cooperation, thus facilitating electricity production and pollutant degradation. In this review, we describe several specific types of EMs and DMs based on their ability to adapt to different environments, and summarize the mechanism of EMs in extracellular electron transfer. The effects of interactions between EMs and DMs are evaluated in terms of electricity production and degradation efficiency. The principle of the enhancement in microbial consortia is also introduced, such as improved biomass, changed degradation pathways, and biocatalytic potentials, which are directly or indirectly conducive to human health.

Elucidating response mechanisms at the metabolic scale of Eisenia fetida in typical oil pollution sites: A native driver in influencing carbon flow.

Previous investigations on the stress response patterns of earthworms (Eisenia fetida) in practical petroleum hydrocarbon (PH) contamination systems were less focused. Therefore, this study investigated the ecotoxicological effect of PH contamination on earthworms based on metabonomics and histological observation, followed by correlation analysis between the earthworm metabolism, PH types and concentrations, soil physicochemical characteristics, and the microbial community structures (i.e., diversity and abundance) and functions. The results showed that due to the abundant PH organics, the cell metabolism of earthworms shifts under PH contamination conditions, leading them to use organic acids as alternative energy sources (i.e., gluconeogenesis pathway). Simultaneously, biomarker metabolites related to cellular uptake, stress response, and membrane disturbance were identified. In addition, when compared to the controls, considerable epicuticle and cuticle layer disruption was observed, along with PH internalization. It was demonstrated that PH pollution preferentially influences the physiological homeostasis of earthworms through indirect (i.e., microbial metabolism regulation) than direct (i.e., direct interaction with earthworms) mechanisms. Moreover, the varied CO2 releasement was verified, which highlights the potential role of earthworms in influencing carbon transformation and corresponds with the considerably enriched energy metabolism-related pathway. This study indicated that PH contamination can induce a strong stress response in earthworms through both direct and indirect mechanisms, which in turn, substantially influences carbon transformation in PH contamination sites.

Diatomic catalysts for Fenton and Fenton-like reactions: a promising platform for designing/regulating reaction pathways.

The optimization of the single-atom catalyst (SAC) performance has been the hot spot for years. It is widely acknowledged that the incorporation of adjacent single-atom sites (diatomic catalysts (DACs)) can enable synergistic effects, which can be used in cascade catalysis, dual-function catalysis, and performance regulation of intrinsic active sites. DACs have been widely applied in the CO2 reduction reaction (CO2RR), oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), etc.; however, their application is limited in Fenton or Fenton-like reactions. This perspective summarizes the most advanced achievements in this field, followed by the proposed opportunities in further research, including regulation of the magnetic moment, inter-atomic distance effect, strain engineering, atomic cluster (AC)/nanoparticle (NP) modification, etc. It is demonstrated that this perspective can contribute to the DAC application in Fenton or Fenton-like reactions with innovative design and mechanisms being put forward.

Potential contribution of chlorella vulgaris to carbon-nitrogen turnover in freshwater ecosystems after a great sandstorm event.

Urban lakes represent important land-water and nature-human dual interfaces that promote the cycling of elements from terrestrials to sediments and consequently modulating the stabilization of regional climate. However, whether disturbances caused by extreme weather events can have substantial effects on carbon-nitrogen (C-N) cycling in these ecosystems are vague. To explore the impact of phytoplankton on the ecological retention time of C-N, two kinds of freshwater (natural and landscape) were collected and conducted a microcosm experiment using a freshwater algal species Chlorella vulgaris. Sandstorm events increased dissolved inorganic carbon in freshwater (65.55 ± 3.09 and 39.46 ± 2.51 mg·L-1 for samples from Jinyang and Nankai, respectively) and significantly affected the relevant pathways of photosynthesis in Chlorella vulgaris, including enhancing chlorophyll fluorescence (The effective quantum yield of PSII at the fifth day of incubation was 0.34 and 0.35 for Nankai and Jinyang, respectively), promoting the synthesis of sugars and inhibiting the synthesis of glycine and serine related proteins. Besides, carbon from plant biomass accumulation and cellular metabolism (fulvic acid-like, polyaromatic-type humic acid and polycarboxylate-type humic acid, etc.) was enriched into residues and become a kind of energy source for the decomposer (TC mass increased by 1.63-2.13 times after 21 days of incubation). This means that the accumulation and consumption of carbon and nitrogen in the residue can be used to track the processes controlling the long-term C-N cycle. Our findings shed light on the plant residues were key factors contributing to the formation of water carbon pool, breaks the traditional theory that dissolved carbonates cannot produce carbon sinks.

Single-cell RNA sequencing revealed subclonal heterogeneity and gene signatures of gemcitabine sensitivity in pancreatic cancer.

Introduction: Resistance to gemcitabine is common and critically limits its therapeutic efficacy in pancreatic ductal adenocarcinoma (PDAC). Methods: We constructed 17 patient-derived xenograft (PDX) models from PDAC patient samples and identified the most notable responder to gemcitabine by screening the PDX sets in vivo. To analyze tumor evolution and microenvironmental changes pre- and post-chemotherapy, single-cell RNA sequencing (scRNA-seq) was performed. Results: ScRNA-seq revealed that gemcitabine promoted the expansion of subclones associated with drug resistance and recruited macrophages related to tumor progression and metastasis. We further investigated the particular drug-resistant subclone and established a gemcitabine sensitivity gene panel (GSGP) (SLC46A1, PCSK1N, KRT7, CAV2, and LDHA), dividing PDAC patients into two groups to predict the overall survival (OS) in The Cancer Genome Atlas (TCGA) training dataset. The signature was successfully validated in three independent datasets. We also found that 5-GSGP predicted the sensitivity to gemcitabine in PDAC patients in the TCGA training dataset who were treated with gemcitabine. Discussion and conclusion: Our study provides new insight into the natural selection of tumor cell subclones and remodeling of tumor microenvironment (TME) cells induced by gemcitabine. We revealed a specific drug resistance subclone, and based on the characteristics of this subclone, we constructed a GSGP that can robustly predict gemcitabine sensitivity and prognosis in pancreatic cancer, which provides a theoretical basis for individualized clinical treatment.

High-dimensional single-cell analysis unveils distinct immune signatures of peripheral blood in patients with pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with poor response to immune checkpoint inhibitors. The mechanism of such poor response is not completely understood. Methods: We assessed T-cell receptor (TCR) repertoire and RNA expression at the single-cell level using high-dimensional sequencing of peripheral blood immune cells isolated from PDAC patients and from healthy human controls. We validated RNA-sequencing data by performing mass cytometry (CyTOF) and by measuring serum levels of multiple immune checkpoint proteins. Results: We found that proportions of T cells (CD45+CD3+) were decreased in PDAC patients compared to healthy controls, while proportion of myeloid cells was increased. The proportion of cytotoxic CD8+ T cells and the level of cytotoxicity per cell were increased in PDAC patients, with reduced TCR clonal diversity. We also found a significantly enriched S100A9+ monocyte population and an increased level of TIM-3 expression in immune cells of peripheral blood in PDAC patients. In addition, the serum level of soluble TIM-3 (sTIM-3) was significantly higher in PDAC patients compared to the non-PDAC participants and correlated with worse survival in two independent PDAC cohorts. Moreover, sTIM-3 exhibited a valuable role in diagnosis of PDAC, with sensitivity and specificity of about 80% in the training and validation groups, respectively. We further established an integrated model by combining sTIM-3 and carbohydrate antigen 19- 9 (CA19-9), which had an area under the curve of 0.974 and 0.992 in training and validation cohorts, respectively. Conclusion: Our RNA-seq and proteomic results provide valuable insight for understanding the immune cell composition of peripheral blood of patients with PDAC.

The optimized Fenton-like activity of Fe single-atom sites by Fe atomic clusters-mediated electronic configuration modulation.

The performance optimization of isolated atomically dispersed metal active sites is critical but challenging. Here, TiO2@Fe species-N-C catalysts with Fe atomic clusters (ACs) and satellite Fe-N4 active sites were fabricated to initiate peroxymonosulfate (PMS) oxidation reaction. The AC-induced charge redistribution of single atoms (SAs) was verified, thus strengthening the interaction between SAs and PMS. In detail, the incorporation of ACs optimized the HSO5- oxidation and SO5·- desorption steps, accelerating the reaction progress. As a result, the Vis/TiFeAS/PMS system rapidly eliminated 90.81% of 45 mg/L tetracycline (TC) in 10 min. The reaction process characterization suggested that PMS as an electron donor would transfer electron to Fe species in TiFeAS, generating 1O2. Subsequently, the hVB+ can induce the generation of electron-deficient Fe species, promoting the reaction circulation. This work provides a strategy to construct catalysts with multiple atom assembly-enabled composite active sites for high-efficiency PMS-based advanced oxidation processes (AOPs).

Enhanced carbon emission driven by the interaction between functional microbial community and hydrocarbons: An enlightenment for carbon cycle.

Soil microbial communities are usually regarded as one of the key players in the global element cycling. Moreover, an important consequence of oil contamination altering the structure of microbial communities is likely to result in an increased carbon emission. However, understanding of the complex interactions between environmental factors and biological communities is clearly lagging behind. Here it showed that the flux of carbon emissions increased in oil-contaminated soils, up to 13.64 g C·(kg soil)-1·h-1. This phenomenon was mainly driven by the enrichment of rare degrading microorganisms (e.g., Methylosinus, Marinobacter, Pseudomonas, Alcanivorax, Yeosuana, Halomonas and Microbulbifer) in the aerobic layer, rather than the anaerobic layer, which is more conducive to methane formation. In addition, petroleum hydrocarbons and environmental factors are equally important in shaping the structure of microbial communities (the ecological stability) and functional traits (e.g., fatty acid metabolism, lipid metabolism and amino acid metabolism) due to the different ecological sensitivities of microorganisms. Thus, it can be believed that the variability of rare hydrocarbon degrading microorganisms is of greater concern than changes in dominant microorganisms in oil-contaminated soil. Undoubtedly, this study could reveal the unique characterization of bacterial communities that mediate carbon emission and provide evidence for understanding the conversion from carbon stores to carbon gas release in oil-contaminated soils.

Efficient electro-catalyzed PMS activation on a Fe-ZIF-8 based BTNAs/Ti anode: An in-depth investigation on anodic catalytic behavior.

Phenanthrene (PHE), mainly released from coal tar and petroleum distillation, is an important kind of prevalent polycyclic aromatic hydrocarbons (PAHs) contamination in China (up to 2.38 ± 0.02 mg/kg in soil and 8668 ng/L in surface water) and other countries in the world. Metal-organic frameworks (MOFs) show promising application prospects in the decontamination field, however, suffering from the intrinsic fragility and fine powder forms. Therefore, macroscopic MOFs architecture-sandwich-like Fe-ZIF-8/blue TiO2 nanotube arrays (BTNAs)/Ti substrate (FBTT) anode with strong interfacial bonding (Fe-O-Ti and Fe-2-MIM-Ti coordination) was constructed using innovative in situ growth, condensation-crystallization-deposition, and pyrolysis methods, aiming at exploring the feasibility of MOFs-based anode/peroxymonosulfate (PMS) mediated PHE elimination, revealing the in-depth mechanisms, simultaneously overcoming the intrinsic drawbacks of MOFs. The FBTT-4 (doping content of 30 %) efficiently degraded PHE by 90.01 % and 74.5 % within 10 min at 350 µg/L and 3 mg/L, respectively, mediated by the ·OH compared to the SO4·-, 1O2, and O2·-. Post-optimized range of anodic potential enabled (i) anodic oxidation, (ii) activation of water and PMS molecules to produce active species, (iii) capture of electrons in reactants to reduce Fe3+/Ti4+ to Fe2+/Ti3+, maintaining the proportion of Fe/Ti with low valence and thus stable PMS activation capacity, and (iv) regulation of the Fe/Ti d-band center to modulate the anode adsorption capacity. The further increment in anodic potential could promote "dark photocatalysis" with a Z-scheme-like mechanism. Thus, it is proposed that the development of macroscopic MOFs-based anode, especially those with small band gaps, represents vast potentials in electrocatalytic contamination elimination. Simultaneously, the MOFs-based anode is expected to fully exploit their catalytic capacities and solve their intrinsic defects as well.

Seasonal disparities and source tracking of airborne antibiotic resistance genes in Handan, China.

The transmission of airborne antibiotic resistance genes (ARGs) loaded on particle is a significant global public health concern. Up to date, the dispersal pattern of airborne ARGs remains unclear despite their critical role in multiregional transmission. In this study, airborne ARGs loaded on fine particulate matter (PM2.5) and source tracking based on the airflow trajectories were performed by the potential source contribution function (PSCF) and concentration weighted trajectory (CWT) model. The results show that the absolute abundance of ARG subtypes were generally twice times higher in the winter season than that in the summer season, which could be attributable to winter haze events with high particulate matter concentrations in Handan. Exogenous input from serious haze events and local release of ARGs loaded on PM2.5 of air masses may cause higher levels of ARGs in the winter. Moreover, based on the positive correlation between the abundance of ARGs and PM2.5 concentration, a source tracing model of airborne ARGs was proposed to the estimate of ARGs release and dissemination. This study highlights airborne ARGs transmission loaded on PM2.5 of air masses, which facilitating the global spread of antibiotic resistance.

Rainfall facilitates the transmission and proliferation of antibiotic resistance genes from ambient air to soil.

Antibiotic resistance is common in bacterial communities and appears to be correlated with human activities. However, the source of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in remote regions remains unclear. In this study, we examined the abundance of ARGs in fine particulate matter (PM2.5) as a carrier throughout the rainfall process (4 mm rain/h) to observe the effects of rainfall on the transmission of ARGs. The results suggested that rainwater served as a reservoir that facilitated the spread of ARGs and that wind and particulate matter (PM) concentrations might be meteorological parameters that influence the distribution of ARGs in rainwater. In addition, soil microcosm experiments were performed to investigate the influence of rainfall on antibiotic resistance in soils with different environmental backgrounds. Rainwater facilitated the proliferation of ARGs and mobile genetic elements (MGEs) from ambient air to soil, and this influence was more obvious in heavy metal-contaminated soil. This is the first study to investigate the routes by which rainfall acts as a mobile reservoir to facilitate the transmission and proliferation of ARGs, and the results indicate the potential source of ARGs in remote regions where humans rarely interfere.

Pollution characteristics and risk assessment of surface sediments in the urban lakes.

The objective of the manuscript was to evaluate the concentration and distribution of nutrients and heavy metals (HMs) in the sediments of urban lakes, as well as the potential ecological risk to the lake. This paper discusses the risk assessment and its management via potential nature-based solutions (NBS), which are lessons learnt from nature. The HM pollution and potential ecological risk were evaluated using conventional geo-accumulation index (GI) and geo-accumulation vector (GV) model. So urban lakes are usually more of a source of pollution than non-urban lakes, and more widely based on the literature on lake sediment pollution assessments in China over the past 10 years, 42 urban lakes, and 5 typical non-urban lakes (five representative freshwater lakes in China) were selected. The average concentrations of total nitrogen (TN); total phosphorus (TP); and Cu, Zn, Pb, Cr, Cd, Ni, As, and Hg were 2382, 712, 33.10, 118.05, 38.30, 66.40, 0.82, 32.38, 11.33, and 0.12 mg/kg, respectively. The pollution levels of nutrients and HMs in sediments were evaluated using a single pollution index, a comprehensive pollution index, a ground accumulation index, a potential ecological risk index, and a sediment quality index. The evaluation results showed that the overall pollution level of urban lake sediments in China was higher than that of the selected five typical non-urban lakes, and the problem of nitrogen pollution in sediments was more prominent. There was no significant difference in the potential risk assessment of HMs between urban lakes and typical non-urban lakes, but the probability of negative biological effects was significant. The surface sediments from the estuaries of the tributaries flowing downtowns and heavy industrial parks showed high heavy metal pollution levels and potential ecological risk. The HM pollution and environmental risk assessment of the sediments from urban lakes is of great significance.

Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer.

OBJECTIVE: V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. METHODS: Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. RESULTS: The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. CONCLUSION: VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.

High-dimensional single-cell analysis delineates radiofrequency ablation induced immune microenvironmental remodeling in pancreatic cancer.

Radiofrequency ablation (RFA) is an effective local therapy approach for treating solitary tumor of many types of malignancy. The impact of RFA on the tumor immune microenvironment on distant tumors after RFA treatment is still unclear. In this study, by using syngeneic tumor models and single-cell RNA and T-cell receptor sequencing, we have investigated the alterations of tumor-infiltrating immune cells in distant non-RFA tumors. Single-cell RNA sequencing identified six distinct lymphoid clusters, five distinct monocyte/macrophage clusters, three dendritic cells clusters, and one cluster of neutrophils. We found that RFA treatment reduced the proportions of immunosuppressive cells including regulatory T cells, tumor-associated macrophages and tumor-associated neutrophils, whereas increased the percentages of functional T cells in distant non-RFA tumors. Moreover, RFA treatment also altered gene expressions in single-cell level in each cell cluster. By using pseudo-time analysis, we have described the biological processes of tumor-infiltrating CD8+ T cells and monocytes/macrophages based on the transcriptional profiles. In addition, the immune checkpoints including PD-1 and LAG3 were upregulated in the T cells in distant non-RFA tumors after RFA treatment. In conclusion, our data indicate that RFA treatment induced remodeling of tumor immune microenvironment in distant non-RFA tumors in pancreatic cancer mouse model and suggest that combining RFA with immune checkpoint inhibitors may be an effective treatment approach.

Heavy metal copper accelerates the conjugative transfer of antibiotic resistance genes in freshwater microcosms.

Recent studies have consistently demonstrated increasing abundances of antibiotic resistance genes (ARGs) in the absence of antibiotic use. There is a large amount of quantitative data that has correlated the elevated ARGs levels with the concentrations of heavy metals in environments with anthropogenic impact. However, the mechanisms by which heavy metals facilitate the proliferation and horizontal gene transfer of ARGs among environmental bacteria were still unknown. This study validated effects of four typical heavy metals (Cu, Cd, Pb, Zn) on the plasmid RP4 mediated conjugative transfer of ARGs in freshwater microcosms. The results suggested that the typical heavy metals including Cu, Pb and Zn would promote conjugative transfer of the plasmid RP4, and Cu (5.0 µg/L) had the greatest ability to increase conjugative transfer by 16-fold higher than the control groups. In conjugative transfer microcosms, the species of each cultivable transconjugant were isolated, and their minimum inhibitory concentrations (MICs) were assessed via antibiotic susceptibility testing. The mechanism of the increased conjugative transfer of Cu was that Cu induced cell damage and the reduced conjugative transfer of Cd was that Cd increased the content of extracellular polymers substances (EPS). This study confirms that heavy metal Cu facilitates the conjugative transfer of environmental-mediated plasmid RP4 by cell damage effect, therefore accelerating the transmission and proliferation of ARGs.

Occurrence and distribution of clinical and veterinary antibiotics in the faeces of a Chinese population.

Antibiotics ingested in the human gut may create selective pressure to change the composition of the gut microbiota, which could adversely effect the immune system of the host. However, the occurrence and distribution of antibiotics in the human gut remains unclear. A total population of 180 individuals, across three Chinses regions with different economic development levels, including children, adults, and elders, were sampled in 2017. A total of 19 representative antibiotics, including both clinical and veterinary antibiotics, were investigated in human faeces. While clinical use and prescriptions were the main exposure pathways for children, environmental media were the exposure pathway to adults. In addition, significant differences (P < 0.05) in antibiotic residues in human faeces were observed amongst various economic development levels, where human faeces from underdeveloped areas were mostly associated with higher levels of antibiotics. This study first to investigate the occurrence and distribution of typical antibiotics in the faeces of a Chinese population and thereby provide a reference for the intensive study of the effects and mechanisms of antibiotics on human gut microbiota.

Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer.

BACKGROUND: Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME. METHODS: Using immunohistochemistry, we examined tumor-infiltrating CD68+ pan-macrophages (CD68+ M) and CD163+ M2 macrophages (CD163+ M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45+ immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline. RESULTS: We found that CD47 expression correlated with the level of CD68+ M but not CD163+ M2. High levels of tumor-infiltrating CD68+ M, CD163+ M2, and CD47 expression were significantly associated with worse survival. CD47high/CD68+ Mhigh and CD47high/CD163+ M2high correlated significantly with shorter survival, whereas CD47low/CD68+ Mlow and CD47low/CD163+ M2low correlated with longer survival. Intriguingly, CD47 blockade decreased the tumor burden in the Panc02 but not in the MPC-83 syngeneic mouse model. Using scRNA-seq, we showed that anti-CD47 treatment significantly remodeled the intratumoral lymphocyte and macrophage compartments in Panc02 tumor-bearing mice by increasing the pro-inflammatory macrophages that exhibit anti-tumor function, while reducing the anti-inflammatory macrophages. Moreover, CD47 blockade not only increased the number of intratumoral CD8+ T cells, but also remodeled the T cell cluster toward a more activated one. Further, combination therapy targeting both CD47 and PD-L1 resulted in synergistic inhibition of PDAC growth in the MPC-83 but not in Panc02 model. MPC-83 but not Panc02 mice treated with both anti-CD47 and anti-PD-L1 showed increased number of PD-1+CD8+ T cells and enhanced expression of key immune activating genes. CONCLUSION: Our data indicate that CD47 targeting induces compartmental remodeling of tumor-infiltrating immune cells of the TME in PDAC. Different PDAC mouse models exhibited differential response to the anti-CD47 and anti-PD-L1 blockade due to the differential effect of this combination treatment on the infiltrating immune cells and key immune activating genes in the TME established by the different PDAC cell lines.