Biology subjects

Jiang, W.

Publications and source records attributed to Jiang, W..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

Derivation of human extended pluripotent stem cells in feeder-free condition

Human extended pluripotent stem cells (EPSCs), with bidirectional chimeric ability to contribute to both embryonic and extra-embryonic lineages, can be obtained and maintained by converting embryonic stem cells (ESCs) using chemicals. However, the transition system is based on inactivated mouse fibroblast, which greatly hinders the mechanistic studies of extended pluripotency and further applications. Here we reported a Matrigel-based feeder-free method to convert human ESCs and iPSCs into EPSCs and demonstrated the extended pluripotency in terms of molecular features, chimeric ability, and transcriptome. We further improved the protocol by applying chemicals targeting glycolysis and histone methyltransferase. Altogether, our data established a feeder-free system to generate human EPSCs and provided additional insights into the acquisition of extended pluripotency.

developmental biology↗

bioRxiv2020

Comparison of methods for estimating genetic correlation between complex traits using GWAS summary statistics

Genetic correlation is the correlation of additive genetic effects on two phenotypes. It is an informative metric to quantify the overall genetic similarity between complex traits, which provides insights into their polygenic genetic architecture. Several methods have been proposed to estimate genetic correlations based on data collected from genome-wide association studies (GWAS). Due to the easy access of GWAS summary statistics and computational efficiency, methods only requiring GWAS summary statistics as input have become more popular than methods utilizing individual-level genotype data. Here, we present a benchmark study for different summary-statistics-based genetic correlation estimation methods through simulation and real data applications. We focus on two major technical challenges in estimating genetic correlation: marker dependency caused by linkage disequilibrium (LD) and sample overlap between different studies. To assess the performance of different methods in the presence of these two challenges, we first conducted comprehensive simulations with diverse LD patterns and sample overlaps. Then we applied these methods to real GWAS summary statistics for a wide spectrum of complex traits. Based on these experiments, we conclude that methods relying on accurate LD estimation are less robust in real data applications compared to other methods due to the imprecision of LD obtained from reference panels. Our findings offer a guidance on how to appropriately choose the method for genetic correlation estimation in post-GWAS analysis in interpretation.

genetics↗

bioRxiv2020

Whole-brain functional connectivity neuromarkers uncover the cognitive recovery scheme for overt hepatic encephalopathy after liver transplantation

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with the overt hepatic encephalopathy (OHE). Liver transplantation (LT) may reverse the impaired brain function. MRI of resting-state functional connectivity can help unravel the underlying mechanisms that lead to these cognitive deficits and recovery. Sixty-four cirrhotic patients (28 with OHE; 36 without) and 32 healthy controls were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated pre- and postsurgical neurocognitive performance in cirrhotic patients using psychomotor tests, i.e. number connection test (NCT) and digit symbol test (DST). Network-based statistics found significant disrupted connectivity in both groups of cirrhosis with OHE and without compared to controls. However, the presurgical connectivity disruption in patients with OHE was included in a greater number of connections than those without (65 vs. 17). The decrease in FC for both OHE and non-OHE patient groups was reversed to the level of controls after LT. An additional hyperconnected network (i.e., higher than controls) was observed in OHE patients after LT (p=0.009). Regarding the neural-behavior relationship, the functional network that predicted cognitive performance in healthy individuals, showed no correlation in presurgical cirrhotic patients. Such an impaired neural-behavior relationship was re-established after LT for non-OHE patients but not for OHE. OHE patients displayed abnormal hyperconnectivity and persistently impaired neural-behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery in comparison to those without, which needs further clarification in the future study.

neuroscience↗

bioRxiv2020

Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry

Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.

cell biology↗

bioRxiv2020

Targeted over-expression of PPARγ in pig skeletal muscle improves oxidative fiber formation and intramuscular fat deposition

PPAR{gamma} is a master regulator of adipogenesis and lipogenesis. To understand its roles in fat deposition and fiber formation in skeletal muscle, we successfully generated muscle-specific overexpression of PPAR{gamma} by pig cloning procedures. The content of intramuscular fat was significantly increased in PPAR{gamma} transgenic pigs while the muscle mass as lean percentage of body weight was not changed. The proteomics analysis demonstrated oxidative metabolism of fatty acids and respiratory chain were increased in PPAR{gamma} pigs. Furthermore, expressions of oxidative muscle fiber-related genes such as MyHC1 and TNNT1 were enhanced. CAMK2, MEF2 and PGC1 were also significantly increased in skeletal muscle of PPAR{gamma} pigs, indicating that Ca2+-sensitive phosphatases and kinases may play an important role in the switch of muscle fiber types when PPAR{gamma} activity is elevated in skeletal muscle. The results support skeletal muscle-specific overexpression of PPAR{gamma} can promote oxidative fiber formation and intramuscular fat deposition in pigs.

genetics↗

bioRxiv2020

A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.

immunology↗

bioRxiv2020

Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice

BACKGROUNDCytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix (ECM) with contractile filaments. During AAA development, (i) aortic medial degeneration is associated with loss of smooth muscle cell (SMC) integrity, and (ii) fibrogenic mesenchymal cells (FMSCs) mediates ECM remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Angiotensin II (AngII)-induced AAAs in low density receptor deficient (LDLR-/-) mice. OBJECTIVESTo evaluate the functional contribution of FMSCs-derived calpain-2 on (i) cytoskeletal structural protein and ECM alterations, and (ii) AAA progression. METHODSCalpain-2 protein, and cytoskeletal protein (e.g. filamin or talin) fragmentation in human and mice AAA tissues were assessed by immunohistochemical and western blot analyses. LDLR-/- mice that were either inducible-whole body or FMSC-specific calpain-2 deficient were fed a fat-enriched diet and infused with AngII for 4 weeks. The association of cytoskeletal protein to ECM was evaluated using aortic SMCs, in vitro. In addition, the effect of calpain-2 deficiency on the stability of established AAA was examined. RESULTSCalpain-2 protein, and filamin/talin fragmentation are significantly elevated in AAAs. Ubiquitous or FMSC-specific depletion of calpain-2 suppressed AngII-induced AAAs, filamin/talin fragmentation and promoted ECM protein, collagen. Calpain-2 silencing in SMCs reduced AngII-induced filamin/talin fragmentation. In addition, silencing of filamin or talin in SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed established AAA rupture. CONCLUSIONCalpain-2 activation promotes cytoskeletal structural protein fragmentation and ECM degradation of experimental AAA aortas. Treatment with calpain-2 specific inhibitor may facilitate the clinical management of AAA.

pathology↗

bioRxiv2020

Asperosaponin VI inhibits LPS-induced inflammatory response by activating PPAR-gamma pathway in primary microglia

Microglia cells are the main mediators of neuroinflammation. Activation of microglia often aggravates the pathological process of various neurological diseases. Natural chemicals have unique advantages in inhibiting microglia-mediated neuroinflammation and improving neuronal function. Here, we examined the effects of asperosaponin VI (ASA VI) on LPS-activated primary microglia. Microglia were isolated from mice and pretreated with different doses of ASA VI, following lipopolysaccharide (LPS) administration. Activation and inflammatory response of microglia cells were evaluated by q-PCR, immunohistochemistry and ELISA. Signaling pathways were detected by western blotting. We found that the ASA VI inhibited the morphological expansion of microglia cells, decreased the expression and release of proinflammatory cytokines, and promoted the expression of antiinflammatory cytokines in a dose-dependent manner. ASA VI also activated PPAR-{gamma} signaling pathway in LPS-treated microglia. The anti-inflammatory effects of ASA VI in microglia were blocked by treating PPAR-{gamma} antagonist (GW9662). These results showed that ASA VI promote the transition of microglia cells from proinflammatory to anti-inflammatory by regulating PPAR-{gamma} pathway.

neuroscience↗

bioRxiv2020

The antidepressant effects of asperosaponin VI are mediated by the suppression of microglial activation and reduction of TLR4/NF-kB induced IDO expression

AimIndoleamine 2, 3-dioxygenase (IDO) is responsible for the progression of the kynurenine pathway, which has been implicated in the pathophysiology of inflammation-induced depression. It has been reported that asperosaponin VI (ASA VI) could play a neuroprotective role through anti-inflammatory and antioxidant. In this study, we examined the antidepressant effect of ASA VI in LPS-treated mice and further explored its molecular mechanism by insight into the microglial kynurenine pathway. MethodsTo produce the model, lipopolysaccharide (LPS) (0.83 mg/kg) was administered intraperitoneally to mice. The mice received ASA VI (10 mg/kg, 20mg/kg, 40mg/kg and 80mg/kg, i.p.) thirty minutes prior to LPS injection. Depressive-like behaviors were evaluated based on the duration of immobility in the forced swim test. Microglial activation and inflammatory cytokines were detected by immunohistochemistry, real-time PCR and ELISA. The TLR4/NF-B signaling pathway and the expression of IDO, GluA2, and CamKII{beta} were measured by western blotting. ResultsASA VI demonstrated significant antidepressant activity in the presence of LPS on immobility and latency times in the forced swim test. The LPS-induced activation of microglia and inflammatory response were inhabited by ASA VI in a dose-dependent manner. TLR4/NF-{kappa}B signaling pathway also was suppressed by ASA VI in the hippocampus and prefrontal cortex of LPS-treated mice. Furthermore, ASA VI inhibited the increase in IDO protein expression and normalized the aberrant glutamate transmission in the hippocampus and prefrontal cortex as a result of LPS administration. ConclusionOur results propose a promising antidepressant effect for ASA VI possibly through the downregulation of IDO expression and normalization of the aberrant glutamate transmission. This remedying effect of ASA VI could be attributed to suppress microglia-mediated neuroinflammatory response via inhibiting the TLR4/NF-{kappa}B signaling pathway.

neuroscience↗

bioRxiv2020

A Piezo1 open state reveals a multi-fenestrated ion permeation pathway

Force-sensing Piezo channels are essential to many aspects of vertebrate physiology. Activation of Piezo1 is facilitated by the presence of negative membrane lipids in the inner leaflet, such as phosphatidylinositol-4,5-bisphosphate (PIP2). Here, to study how Piezo1 opens, we performed molecular dynamics simulations of Piezo1 in membranes flattened by the periodic boundary effect and with or without PIP2 lipids. The Piezo1 pore spontaneously opens in the asymmetrical bilayer but not in the symmetric membrane or when PIP2 lipids are neutralized. Electrophysiological characterization of putative PIP2-interacting Piezo1 residues suggests the contribution of multiple PIP2 binding sites. Our Piezo1 open state recapitulates ionic selectivity, unitary conductance and mutant phenotypes obtained from numerous experimental studies. Tracking ion diffusion through the open pore reveals the presence of intracellular and extracellular fenestrations, delineating a multi-fenestrated permeation pathway. This open state sheds light on the mechanisms of lipid modulation, permeation, and selectivity in a Piezo channel.

biophysics↗

bioRxiv2020

Developing an endogenous quorum-sensing based CRISPRi circuit for autonomous and tunable dynamic regulation of multiple targets in industrial Streptomyces

Dynamic regulation has emerged as an effective strategy to improve product titers by balancing metabolic networks, which can be implemented by coupling gene expression to pathway-independent regulatory elements, such as quorum-sensing (QS) systems. However, these QS-based circuits are often created on heterologous systems and must be carefully tuned through tedious testing and optimization process to make them work well, which hampers their application in industrial microbes including streptomycetes. In this study, we design a pathway-independent QS circuit by directly integrating an endogenous QS system with CRISPRi (named EQCi) in the industrial rapamycin-producing strain Streptomyces rapamycinicus. EQCi has the advantages of both the QS system and CRISPRi, which enables tunable, fully autonomous and dynamic regulation of multiple targets simultaneously. To demonstrate its effectiveness, we downregulate three key nodes in essential pathways separately to divert metabolic flux toward rapamycin biosynthesis. In each case, significant increases in rapamycin titers are achieved. We further apply EQCi to simultaneously control these three key nodes with proper repression strength by changing sgRNA targeting positions. The final rapamycin titer reaches to 1836{+/-}191 mg/L, which is the highest reported titer. Notably, compared to traditional static engineering strategy, which result in growth arrest and suboptimal rapamycin titers, EQCi regulation substantially promote rapamycin titers without affecting cell growth, which indicates that it can achieve the trade-off between essential pathways and product synthesis. Collectively, this study provides a simple and effective strategy for optimizing product titers and may have the potential to apply to other industrial microorganisms.

bioengineering↗

bioRxiv2019

Prokaryotic Single-Cell RNA Sequencing by In Situ Combinatorial Indexing

Despite longstanding appreciation of gene expression heterogeneity in isogenic bacterial populations, affordable and scalable technologies for studying single bacterial cells have been limited. While single-cell RNA sequencing (scRNA-seq) has revolutionized studies of transcriptional heterogeneity in diverse eukaryotic systems, application of scRNA-seq to prokaryotes has been hindered by their extremely low mRNA abundance, lack of mRNA polyadenylation, and thick cell walls. Here, we present Prokaryotic Expression-profiling by Tagging RNA In Situ and sequencing (PETRI-seq), a low-cost, high-throughput, prokaryotic scRNA-seq pipeline that overcomes these technical obstacles. PETRI-seq uses in situ combinatorial indexing to barcode transcripts from tens of thousands of cells in a single experiment. PETRI-seq captures single cell transcriptomes of Gram-negative and Gram-positive bacteria with high purity and low bias, with median capture rates >200 mRNAs/cell for exponentially growing E. coli. These characteristics enable robust discrimination of cell-states corresponding to different phases of growth. When applied to wild-type S. aureus, PETRI-seq revealed a rare sub-population of cells undergoing prophage induction. We anticipate broad utility of PETRI-seq in defining single-cell states and their dynamics in complex microbial communities.

systems biology↗

bioRxiv2019

Structural Brain Alterations and Their Association with Cognitive Function and Symptoms in Attention-Deficit/Hyperactivity Disorder Families

Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 - 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a case/control difference with sub-clinical cases being intermediate between cases and controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to cases, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.

neuroscience↗

bioRxiv2019

High-fidelity continuum modeling predicts voiced sound production

Voiced sound production is the primary form of acoustic communication in terrestrial vertebrates, particularly birds and mammals, including humans. Developing a causal physics-based model that links descending vocal motor control to tissue vibration and sound requires embodied approaches that include realistic representations of voice physiology. Here we first implement and then experimentally test a high-fidelity three-dimensional continuum model for voiced sound production in birds. Driven by individual-based physiologically quantifiable inputs, combined with non-invasive inverse methods for tissue material parameterization, our model accurately predicts observed key vibratory and acoustic performance traits. These results demonstrate that realistic models lead to accurate predictions and support the continuum model approach as a critical tool towards a causal model of motor control of voiced sound production.

zoology↗

bioRxiv2019

Individualized ctDNA Fingerprints to Monitor Treatment Response and Recurrence in Multiple Cancer Types

Circulating tumor DNA (ctDNA) panels hold high promise of accurately predicting the therapeutic response of tumors while being minimally invasive and cost-efficient. However, their use has been limited to a small number of tumor types and patients. Here, we developed individualized ctDNA fingerprints suitable for most patients with multiple cancer types. The panels were designed based on individual whole-exome sequencing data in 521 Chinese patients and targeting high clonal population clusters of somatic mutations. Together, these patients represent 12 types of cancers and seven different treatments. The customized ctDNA panels have a median somatic mutation number of 19, most of which are patient-specific rather than cancer hotspot mutations; 66.8% of the patients were ctDNA-positive. We further evaluated the ctDNA content fraction (CCF) of the mutations, and analyzed the association between the change of ctDNA concentration and therapeutic response. We followed up 106 patients for clinical evaluation, demonstrating a significant correlation of changes in ctDNA with clinical outcomes, with a consistency rate of 93.4%. In particular, the median CCF increased by 204.6% in patients with progressive disease, decreased by 82.5% in patients with remission, and was relatively stable in patients with stable disease. Overall, 85% of the patients with a ctDNA-positive status experienced metastasis or relapse long before imaging detection, except for two patients who developed recurrence and metastasis almost simultaneously. The average lead time between the first ctDNA-positive finding and radiological diagnosis was 76 days in three patients that changed from a ctDNA-negative to -positive status. Our individualized ctDNA analysis can effectively monitor the treatment response, metastasis, and recurrence in multiple cancer types in patients with multiple treatment options, therefore offering great clinical applicability for improving personalized treatment in cancer.\n\nOne Sentence SummaryctDNA fingerprint panels were customized to predict the treatment response for multiple cancer types from individual whole-exome sequencing data.

cancer biology↗

bioRxiv2019

Cas12a-based on-site and rapid nucleic acid detection of African swine fever

The mortality rate of hemorrhagic African swine fever (ASF), which targets domestic pigs and is caused by African swine fever virus (ASFV), can reach 100%. ASF has been reported in 25 Chinese provinces since August 2018. There is no effective treatment or vaccine for it and the present molecular diagnosis technologies have trade-offs in sensitivity, specificity, cost and speed, and none of them cater perfectly to ASF control. Thus, a technology that overcomes the need for laboratory facilities, is relatively low cost, and rapidly and sensitively detects ASFV would be highly valuable. Here, we describe an RAA-Cas12a-based system that combines recombinase-aided amplification (RAA) and CRISPR/Cas12a for ASFV detection. The fluorescence intensity readout of this system detected ASFV p72 gene levels as low as 10 aM. For on-site ASFV detection, lateral-flow strip readout was introduced for the first time in the RAA-Cas12a based system (named CORDS, Cas12a-based On-site and Rapid Detection System). We used CORDS to detect target DNA highly specifically using the lateral-flow strip readout. CORDS could identify the p72 gene at femtomolar sensitivity in an hour at 37{degrees}C, and only requires an incubator. For ease of use, the regents of CORDS was lyophilized to three tubes and remained the same sensitivity when stored at 4 {degrees}C for at least 7 days. Thus, CORDS provides a rapid, sensitive and easily operable method for ASFV on-site detection. Lyophilized CORDS can withstand long-term transportation and storage, and is ready for field applications.

molecular biology↗

bioRxiv2019

A visualizable hepatitis A virus and hepatitis C virus coinfection model in vitro: coexistence of two hepatic viruses under limited competition in viral RNA synthesis

Hepatitis A virus (HAV) and hepatitis C virus (HCV) coinfection in patients usually leads to HCV suppression or clearance. Whether this suppression/clearance is caused by direct virus-virus interaction or indirect interactions is still unknown. Here, we present a robust and visualizable HAV/HCV coinfection model for investigating their interactions in vitro. We find that HAV super infects HCV-persistently-infected Huh-7.5.1 cells without obvious virus-virus exclusion and vice versa, while there is a mild reciprocal viral interference in coinfection. Through single-cell scale confocal microscopy analysis and treating co-infected cells with rNTPs or antivirals e.g. Sofosbuvir, Simeprevir, and Ledipasvir, we find that HAV and HCV exploit cellular machinery in a compatible manner, but with reciprocal competition for rNTPs in their RNA synthesis. In conclusion, our findings reveal the absence of direct HAV-HCV interaction but the presence of indirect interaction, which may be due to limited competition in viral RNA synthesis. Therefore, we propose that suppression/clearance of HCV in HAV/HCV coinfected patients is probably due to indirect interactions e.g. viral competition or immunological interactions.\n\nAuthor summaryVirus-virus interactions could usually be categorized in three aspects: (1) direct interaction induced by interaction of viral gene or gene products; (2) indirect interaction mediated by immune response or (3) host environmental alteration. Hepatitis A virus (HAV) and hepatitis C virus (HCV) are two important causatives of human hepatitis. In patients, their coinfection often induces HCV suppression/clearance, and sometimes may lead to fulminant hepatitis. In this study, we find that a limited reciprocal viral interference occurs in HAV/HCV coinfection in vitro, which results from a viral competition of rNTPs in viral RNA synthesis. Our study provides a new paradigm of studying virus-virus interactions in single-cell scale. To our knowledge, we identify the rNTPs competition in virus coinfection for the first time by experiment, though several mathematical modelings have predicted the resource competition in virus coinfection.

microbiology↗

bioRxiv2019

CD155/CD96 promotes immunosuppression in lung adenocarcinoma (LUAD)

Lung adenocarcinoma (LUAD) remains one of the leading causes of death in patients with cancer. The association of CD155 with CD96 transmits an inhibitory signal and suppresses antitumor immune response. This study investigates the effect of CD155/CD96 on immune suppression in LUAD. We demonstrate that LUAD patients with high CD155 expression suffer from immune suppression and experience a poor prognosis, which coincides with an inhibited AKT-mTOR signaling pathway in CD8 T cells and subsequently up-regulated CD96 expression. Moreover, the inhibition effect can be reversed by CD96 blocking antibody. High CD155 expression inhibited the release of IFN{gamma} from CD8 cells. Moreover, Blocking CD96 restored IFN{gamma} production in CD8 T cells and neutralized the inhibition of IFN{gamma} production in CD8 T cells mediated by CD155. Animal experiments showed that CD155-mediated LUAD growth might depend on its suppression antitumor immune response in the tumor microenvironment in PDX mice. In conclusion, our results suggest that LUAD cells suppress antitumor immune response in the tumor microenvironment through CD155/CD96. CD155/CD96 could be a potential therapeutic target for LUAD patients.\n\nAbbreviationsLUAD: lung adenocarcinoma; IFN{gamma}: interferon gamma; PDX: patient-derived xenograft; NSCLC: non-small cell lung cancer; PRR: poliovirus receptor-related; MDSCs: myeloid-derived suppressor cells; PRR: poliovirus receptor-related; STR: short tandem repeat; IRS: immunoreactive score; SI: staining intensity; PP: percentage of positive cells; RT-PCR: reverse transcription-polymerase chain reaction; PBS: phosphate-buffered saline; PBMCs: peripheral blood mononuclear cells; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; rCD155: recombinant human CD155; LUAD cells: lung adenocarcinoma cells; TILs: tumor-infiltrating lymphocytes; GzmB: granzyme B; IL-2 (Interleukin-2); TNF- : tumor necrosis factor-alpha; PI: propidium Iodide; PDX: patient-derived xenograft; TIGIT: T cell immunoreceptor with Igand ITIM domains; WBC: white blood cells; MFI: mean fluorescence intensity; HPF: high power field

cancer biology↗