Biology subjects

Tran, E.

Publications and source records attributed to Tran, E..

At least 19 recordsLinked to original sources

bioRxiv2026

neissflow: Streamlining Genomic Epidemiology of Neisseria gonorrhoeae with Nextflow

Antimicrobial-resistant Neisseria gonorrhoeae (Ng) poses a growing global public health threat. Existing tools available for Ng genome analysis carry notable limitations, including incomplete resistance marker coverage, absence of species identification, and lack of phylogenetic capability. We developed neiss-flow, a highly parallelized Nextflow pipeline for Ng genome analysis that integrates five subworkflows: read preprocessing, species identification, de novo assembly, antimicrobial resistance (AMR) profiling, and recombination-aware phylogenetic analysis with outbreak detection. neissflow performs extensive quality control on reads, assemblies, variant calls, and phylogenetic results. Validation was performed on two datasets: a mixed-species dataset (n=158; 105 Ng and 53 non-gonococcal species) for sensitivity/specificity assessment, and a reproducibility dataset (n=283 replicate sequences from 17 reference strains) for consistency and phylogenetic validation. neissflow achieved 100% sensitivity and specificity for Ng species identification compared with MALDI-TOF and PubMLST methods. All nine AMR and typing analytes demonstrated [≥]98.1% concordance with PubMLST genotype calls. Genotype-phenotype validation confirmed perfect concordance for key resistance determinants including gyrA mutations with ciprofloxacin resistance, 23S rRNA mutations with high-level azithromycin resistance, and tetM plasmid gene with high-level tetracycline resistance. Reproducibility analysis demonstrated 99.97% concordance across 3,093 analyte calls. Phylogenetic validation demonstrated 100% accuracy for both strain-level and intra-MLST clustering. neissflow is a robust, accessible, and standardized pipeline, positioning it as a valuable tool for public health laboratories engaged in Ng AMR monitoring and outbreak investigations. ImportanceNeisseria gonorrhoeae (Ng) is the second most common reported bacterial sexually transmitted infection and has developed resistance to all clinically relevant antibiotics. Surveillance of Ng resistance informs clinical recommendations for treatment of gonococcal infections. Whole genome sequencing (WGS) offers powerful insights into resistance mechanisms and transmission dynamics. However, many public health laboratories lack the resources needed to analyze these data effectively. We developed neissflow as an end-to-end, accessible Ng WGS analysis pipeline. neissflow demonstrated exceptional accuracy and reproducibility across diverse reference datasets. neissflow enables broader adoption of whole-genome sequencing-based surveillance and supports timely public health responses to emerging antimicrobial resistance in Ng by lowering technical barriers.

bioinformatics↗

bioRxiv2026

Organoid modeling of tumor-associated macrophages reveals phagocytosis checkpoint blockade-induced conversion to an immunosuppressive SPP1+ phenotype

Tumor-associated macrophages (TAM) exert essential functions during the immune response to cancer. However, investigations of TAM within a native human tumor microenvironment (TME) have been impeded by a lack of appropriate model systems. Here, patient-derived organoids (PDO) from air-liquid interface (ALI)-grown tumor fragments, containing a human TME that encompassed stroma and immune subsets, robustly preserved TAM that were maintained by endogenous CSF-1 and appropriately responded to polarization signals. Antibody blockade of the CD47 regulatory checkpoint in organoids stimulated phagocytosis and remodeled TAM cytokine secretion profiles that were confirmed in anti-CD47 phase I trial patients. Amongst PDO histologies screened, anti-CD47 tumor killing was notable in clear cell renal cell carcinoma (ccRCC) which was associated with increased TAM infiltration. PDO contained diverse previously described TAM subsets; however, anti-CD47 reprogrammed organoid TAM toward an immunosuppressive SPP1+ phenotype, highlighting a negative feedback mechanism. Our findings uncover a resistance circuit engaged by macrophage checkpoint blockade and position ALI PDO as a robust translational platform for dissecting human macrophage biology and informing precision immunotherapy.

cancer biology↗

bioRxiv2026

Ecological context structures duplication and mobilization of antibiotic and metal resistance genes in bacteria

Antibiotic resistance is a global challenge driven by the persistence and spread of resistance genes across ecological contexts. While mobile genetic elements (MGEs) facilitate horizontal gene transfer, gene duplication represents an additional mechanism through which resistance genes can be amplified, diversified, and maintained under selection. How these processes interact across environments remains poorly understood. Here, we examined genome-level patterns of resistance gene abundance, duplication, and mobilization across clinical, agricultural, and wastewater settings, focusing on both antibiotic resistance genes (ARGs) and metal resistance genes (MRGs). Resistance gene profiles were strongly structured by environment, with distinct duplication patterns emerging across sources. Duplicate genes were frequently associated with MGEs, although the strength of this relationship varied by resistance type and ecological context. Despite frequent co-occurrence of ARGs and MRGs, their duplication and mobilization dynamics were not uniformly coupled at the genome level. Together, these findings highlight gene duplication as a context-dependent contributor to resistance evolution and underscore the importance of ecological setting in shaping how resistance genes persist and spread across microbial communities.

bioinformatics↗

bioRxiv2025

Single-cell neural network classifiers reveal that PM21 NK cell expansion is dependent on B cell signaling

In the field drug development ML/AI methods are being applied to improve drug production speed, costs, and reliability. In allogenic NK cell therapy production, one of the biggest challenges is the inherent variability in the donors that provide the starting material for NK cell expansion. In this study we performed PM21-mediated NK cell expansion on 26 donors, and in parallel performed single-cell transcriptomics on the same donor sample prior to expansion. Canonical differential expression analysis and cell state abundance did not highlight any significant difference between donors with high and low NK cell expansion yield. Instead, training neural networks classifiers for high-yield donors enabled identifying several highly predictive models with perfect cross-validation recall. Further investigation of the most predictive models unveiled a previously unknown role for B cell in supportive NK cell expansion. Overall, this study represents a blueprint for combining deep phenotyping and machine learning methods to unveil novel biology and improve the quality and speed of delivery of cell therapeutics to patients.

systems biology↗

bioRxiv2025

Intestinal catabolism of dietary fructose promotes obesity and insulin resistance via ileal lacteal remodeling

High-fructose corn syrup (HFCS) consumption is a risk factor for obesity and metabolic syndrome, yet the underlying mechanisms are incompletely understood. Catabolism of dietary fructose primarily occurs in the small intestine and liver, with fructose breakdown in the liver being pathological, while small intestinal fructose clearance protects the liver. Here, we unexpectedly found that inhibition of fructose catabolism specifically in the small intestine mitigates fructose-induced obesity and insulin resistance. Mechanistically, blocking intestinal fructose catabolism reduces dietary fat absorption, which is associated with a decrease in the surface area of the ileal lacteals and alterations in gut microbiome. Fecal transplantation experiments revealed that such a microbiome stimulates the intestine-resident macrophages, promoting lacteal growth and boosting dietary fat absorption. Given the preclinical and clinical studies reporting the effect of fructose catabolism suppression on mitigating diet-induced obesity, our data suggest that such effects are partly mediated by intestinal lacteal remodeling. Significance StatementHere, we uncover a previously unappreciated link between intestinal fructose catabolism and ileal lacteal remodeling, suggesting the mechanisms by which fructose intake promotes obesity. Using mice lacking the fructose-processing enzyme specifically in the intestine, we show that blocking intestinal fructose metabolism protects against diet-induced obesity by reducing fat absorption. Changes in gut microbiome and immune cell interactions drive this effect.

physiology↗

bioRxiv2025

Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia

Aberrant activation of the RAS/MAPK signaling limits the clinical efficacy of several targeted therapies in acute myeloid leukemia (AML). In FLT3-mutant AML, the selection of clones harboring heterogeneous RAS mutations drives resistance to FLT3 inhibitors (FLT3i). RAS activation is also associated with resistance to other AML targeted therapies, including the BCL2 inhibitor venetoclax. Despite the critical need to inhibit RAS/MAPK signaling in AML, no targeted therapies have demonstrated clinical benefit in RAS-driven AML. To address this unmet need, we investigated the preclinical activity of RMC-7977, a multi-selective inhibitor of GTP-bound active [RAS(ON)] isoforms of mutant and wild-type RAS in AML models. RMC-7977 exhibited potent antiproliferative and pro-apoptotic activity across AML cell lines with MAPK-activating signaling mutations. In cell line models with acquired FLT3i resistance due to secondary RAS mutations, treatment with RMC-7977 restored sensitivity to FLT3i. Similarly, RMC-7977 effectively reversed resistance to venetoclax in RAS-addicted cell line models with both RAS wild-type and mutant genetic backgrounds. In murine patient-derived xenograft models of RAS-mutant AML, RMC-7977 was well tolerated and significantly suppressed leukemic burden in combination with gilteritinib or venetoclax. Our findings strongly support clinical investigation of broad-spectrum RAS(ON) inhibition in AML to treat and potentially prevent drug resistance due to activated RAS signaling.

cancer biology↗

bioRxiv2025

Active learnings impact on student course performance in STEM varies by type and intensity

We updated a recent meta-analysis of active learnings impact on student achievement in undergraduate STEM courses by following the same protocol to evaluate studies published from 2010-2017. We screened 1659 papers, coded 1294, and found 210 that met five pre-established inclusion criteria and six pre-established criteria for methodological quality. After further dropping 76 studies with no exam scores data, 134 of these studies contained data on student performance on identical or equivalent exams. We found that on average, active learnings effect size on exam scores was 0.519 {+/-} 0.049, meaning that when students are in active learning classes, they perform roughly half a standard deviation higher on an identical exam. Funnel plots and sensitivity analyses indicated that these results were not due to sampling bias. Active learning had a positive impact on student outcomes regardless of class size, course level, or STEM discipline, though there was heterogeneity in the effects. All of these results are very similar when compared to earlier meta-analyses, however increased resolution in the studies analyzed here revealed two novel results. First, student performance was significantly better in courses that employed high-intensity active learning, defined as students being on task at least two-thirds of class time, versus lower-intensities. Additionally, there was significant heterogeneity in efficacy across different types of active learning employed. These results suggest that most, if not all types of active learning are effective, and that when innovating in their classes, instructors should continually work to increase active learning intensity. We urge caution in interpreting the results on active learning types, however, and propose a preliminary framework for making more-sophisticated and reliable analyses of variation in course design. Finally, the evidence presented here for active learnings impact on student outcomes creates a strong foundation for faculty professional development and administration.

scientific communication and education↗

bioRxiv2025

Using Fiji as a simplified tool for assessing alveolar chord length and septal thickness in neonatal pulmonary disease research

Bronchopulmonary Dysplasia (BPD) is a neonatal condition primarily affecting babies born prematurely, who have been exposed to invasive ventilation and/or oxygen supplementation. These therapies predispose the immature developing lungs to inflammation and injury to the alveolar epithelium resulting in loss of the alveolar epithelium and thickening of alveolar septa, the 2 important hallmarks of the pathology of BPD. The expansion and enlargement of the alveolar sacs gives the characteristic feature of alveolar simplification in BPD. To measure this alveolar abnormality, we have modified and developed a custom-made Chord Length Fiji plugin which can easily measure the Chord Length and Septal Thickness on Hematoxylin-Eosin-stained histological lung sections, thus generating an instant morphometry readout for quick interpretation. We validated this plugin in multiple animal experimental models and human neonatal lungs with BPD. We were able to differentiate the morphology under conditions of ventilation or hyperoxia exposure, when compared with untreated controls. We thus conclude that our Chord Length and Septal Thickness plugin can be used in a simplified manner following a less meticulous automated operation. To facilitate global use, we have created a DOI so that any user can access it without any restrictions to complete the morphometric measurements. This plugin will be useful for smaller research laboratories with limited budgets and require no access to complex software.

pathology↗

bioRxiv2025

A systematic review of climate-change driven range shifts in mosquito vectors

As global temperatures rise, concerns about shifting mosquito ranges--and accompanying changes in the transmission of malaria, dengue, and other diseases--are mounting. However, systematic evidence for climate-driven changes in mosquito ranges remains limited. We conducted a systematic review of studies documenting expansions or contractions in medically important mosquito species. In total, 178 studies on six continents identified range expansions in 118 mosquito species. While over a third of these studies cited warming as a driver, fewer than 10% performed statistical tests of the role of climate. Instead, most expansions were linked to human-aided dispersal (e.g., trade, travel), land-use changes, and urbanization. Although several studies reported poleward or upward expansions consistent with climate warming, none demonstrated warm-edge contractions driven by rising temperatures, which are theoretically predicted in some settings. Rather than expanding into newly suitable areas, many expansions appear to be filling preexisting thermally suitable habitats. Our findings highlight the need for long-term mosquito monitoring, rigorous climate-attribution methods, and better documentation of confounding factors like land-use change and vector control efforts to disentangle climate-driven changes from other anthropogenic factors.

ecology↗

bioRxiv2025

RAS pathway activation drives clonal selection and monocytic differentiation in FLT3 and BCL2 inhibitor resistance

Despite efficacy of FLT3 and BCL2 inhibition in acute myeloid leukemia (AML), relapse limits survival. Mutation status and AML monocytic differentiation are implicated in resistance. On-treatment tumor evolution may select for genetically distinct clones or shifts in differentiation not resolvable by bulk sequencing. We performed multiomic single cell (SC) DNA/protein and RNA/protein profiling of patients treated on a clinical trial of the BCL2 inhibitor venetoclax and the FLT3 inhibitor gilteritinib (Ven/Git) to characterize immunophenotypic, transcriptional, and genetic clonal evolution on therapy. We found that while Ven/Gilt effectively eliminated FLT3 mutant clones, it selected for RAS mutations, RAS pathway activation and RAS-associated monocytic differentiation. In an in vitro model of monocytic differentiation associated with heightened RAS pathway activation, we demonstrated that MEK inhibition re-sensitized to Ven/Gilt. These data indicate RAS signaling is central to FLT3 and BCL2 inhibitor resistance, is tightly coupled to monocytic differentiation and can be overcome by RAS pathway inhibition. COIC.C.S. has provided educational talks for Astellas Pharma, served on advisory boards for Genentech/Abbvie and received research funding from Abbvie. B.C., Y.S. and J.H. are employees of Abbvie. M.S. and H.H. are or were previously employees of Genentech. FundingThis work was supported in part by Abbvie. C.C.S. is a Leukemia & Lymphoma Society Scholar in Clinical Research and a Damon Runyon-Richard Lumsden Foundation Clinical Investigator supported (in part) by the Damon Runyon Cancer Research Foundation (CI-99-18). Statement of SignificanceMutational and non-mutational RAS signaling activation drives clonal selection, monocytic differentiation and treatment resistance to FLT3 and BCL2 inhibition in AML. MEK inhibition can resensitize resistant AML cells, suggesting therapeutic potential for combined FLT3, BCL2 and RAS pathway inhibition in AML.

cancer biology↗

bioRxiv2024

Covalent inhibitors of the RAS binding domain of PI3Ka impair tumor growth driven by RAS and HER2

Genetic disruption of the RAS binding domain (RBD) of PI 3-kinase (PI3K) prevents the growth of mutant RAS driven tumors in mice and does not impact PI3Ks role in insulin mediated control of glucose homeostasis. Selectively blocking the RAS-PI3K interaction may represent an attractive strategy for treating RAS-dependent cancers as it would avoid the toxicity associated with inhibitors of PI3K lipid kinase activity such as alpelisib. Here we report compounds that bind covalently to cysteine 242 in the RBD of PI3K p110 and block the ability of RAS to activate PI3K activity. These inhibitors have a profound impact on the growth of RAS mutant and also HER2 over-expressing tumors, particularly when combined with other inhibitors of the RAS/MAPK pathway, without causing hyperglycemia.

cancer biology↗

bioRxiv2024

Suppression of NRF2-dependent cancer growth by a covalent allosteric molecular glue

The NRF2 transcription factor is constitutively active in cancer where it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2-dependency and resistance to chemo/radiotherapy. Here we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the KEAP1-CUL3 ubiquitin-ligase complex. VVD-065 specifically and covalently engages C151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported C151-directed compounds decrease KEAP1-CUL3 interactions and stabilize NRF2, thus establishing KEAP1_C151 as a tunable regulator of the KEAP1-CUL3 complex and NRF2 stability. VVD-065 inhibited NRF2-dependent tumor growth and sensitized cancers to chemo/radiotherapy, supporting an open Phase I clinical trial (NCT05954312).

cancer biology↗

bioRxiv2024

Analyzing Biodiversity in Protected vs. Unprotected Tide Pools

This study assessed the efficacy of marine protected areas (MPAs) by comparing tide pool biodiversity in Half Moon Bay, California between a protected site (Fitzgerald Marine Reserve) and an unprotected site (Mavericks Beach). Samples were collected through random quadrat surveys. ImageJ and RStudio were used to analyze data through three methods utilizing the Simpsons Diversity Index along with three metrics. The unprotected Mavericks Beach displayed greater biodiversity through two metrics while the third did not find significant difference in biodiversity between sites. 30 unique species were present at each site with 43 species between both. These mixed findings prevent us from drawing definitive conclusions on the effectiveness of Half Moon Bays tide pool MPAs but suggest the MPA is less biodiverse. Potential explanations include the Intermediate Disturbance Hypothesis, lack of sample size, or that the MPA is not effective in maintaining biodiversity.

ecology↗

bioRxiv2024

The Human Neural Cell Atlas of Zika Infection in developing human brain tissue: viralpathogenesis, innate immunity, and lineage reprogramming

Zika virus (ZIKV) infection during pregnancy can lead to fetal brain infection and developmental anomalies collectively known as congenital Zika syndrome (CZS). To define the molecular features underlying CZS in a relevant human cell model, we evaluated ZIKV infection and neurodevelopment in primary fetal brain explants and induced pluripotent stem cell-derived mixed neural cultures at single cell resolution. We identified astrocytes as key innate immune sentinel cells detecting ZIKV and producing IFN-{beta}. In contrast, neural progenitor cells displayed impaired innate immunity and supported high levels of viral replication. ZIKV infection of neurons suppressed differentiation and synaptic signaling networks and programmed a molecular switch from neurogenesis to astrogliogenesis. We identified a universal ZIKV-driven cellular stress response linked to intrinsic apoptosis and regulated by IFN-{beta}. These findings reveal how innate immune signaling intersects with ZIKV-driven perturbations in cellular function to influence CZS outcomes including neuron developmental dysfunction and apoptotic cell death.

immunology↗

bioRxiv2024

Antigen-specificity of clonally-enriched CD8+ T cells in multiple sclerosis

CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naive MS patients and control participants. A small subset of highly expanded and activated CD8+ T cells were enriched in the CSF in MS that displayed high activation, cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. These findings shed vital insight into the role of CD8+ T cells in MS and pave the way towards disease biomarkers and therapeutic targets. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/611010v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a0b738org.highwire.dtl.DTLVardef@5cf5c2org.highwire.dtl.DTLVardef@10abdccorg.highwire.dtl.DTLVardef@32c7b2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical SummaryC_FLOATNO Created in BioRender. Sabatino, J. (2024) BioRender.com/e66l598 C_FIG

immunology↗

bioRxiv2024

Single Nucleotide Polymorphism (SNP) and Antibody-based Cell Sorting (SNACS): A tool for demultiplexing single-cell DNA sequencing data

MotivationRecently, single-cell DNA sequencing (scDNA-seq) and multi-modal profiling with the addition of cell-surface antibodies (scDAb-seq) have provided key insights into cancer heterogeneity. Scaling these technologies across large patient cohorts, however, is cost and time prohibitive. Multiplexing, in which cells from unique patients are pooled into a single experiment, offers a possible solution. While multiplexing methods exist for scRNAseq, accurate demultiplexing in scDNAseq remains an unmet need. ResultsHere, we introduce SNACS: Single-Nucleotide Polymorphism (SNP) and Antibody-based Cell Sorting. SNACS relies on a combination of patient-level cell-surface identifiers and natural variation in genetic polymorphisms to demultiplex scDNAseq data. We demonstrated the performance of SNACS on a dataset consisting of multi-sample experiments from patients with leukemia where we knew truth from single-sample experiments from the same patients. Using SNACS, accuracy ranged from 0.948 - 0.991 vs 0.552 - 0.934 using demultiplexing methods from the single-cell literature. Availability ImplementationSNACS is available at https://github.com/olshena/SNACS. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/579345v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1e52aaorg.highwire.dtl.DTLVardef@c51d1dorg.highwire.dtl.DTLVardef@fa68a6org.highwire.dtl.DTLVardef@1ec6bd1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

Auranofin induces lethality driven by reactive oxygen species in high-grade serous ovarian cancer cells

High-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer cases in the clinical setting; the survival rate for this disease remains remarkably low due to the lack of long-term consolidation therapies following the standard platinum-based chemotherapy, which is not long lasting as the disease recurs as platinum resistant. The purpose of this study was to explore a novel treatment against HGSOC using the gold complex auranofin (AF). AF primarily functions as a pro-oxidant agent through the inhibition of thioredoxin reductase (TrxR), an antioxidant enzyme that is overexpressed in ovarian cancer. We investigated the effect of AF on TrxR activity and various mechanisms of cytotoxicity using HGSOC cells that are clinically sensitive or resistant to platinum. In addition, we studied the interaction between AF and another pro-oxidant agent, L-buthionine sulfoximine (L-BSO), an anti-glutathione (GSH) compound. We demonstrate that AF potently inhibits TrxR activity and reduces the vitality and viability of HGSOC cells regardless of their sensitivities to platinum. We show that AF induces accumulation of reactive oxygen species (ROS), triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis. Yet, AF-induced cell death is abrogated by the ROS-scavenger N-acetyl cysteine (NAC). In addition, the lethality of AF is associated with the activation of caspases-3/7 and the generation of DNA damage, effects that are also prevented by the presence of NAC. Finally, when AF and L-BSO are combined, we observed a synergistic lethality against HGSOC cells, which is mediated by a further increase in ROS together with a decrease in the levels of the antioxidant GSH. In summary, our results support the concept that AF can be used alone or in combination with L-BSO to kill HGSOC cells regardless of their platinum sensitivities suggesting that depletion of antioxidants is an efficient route for treating this disease.

cancer biology↗

bioRxiv2023

A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity

The inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors could be ascribed to the inhibition of PTP1B/PTPN2 in T cells, whereas in cold tumors, Compound-182 elicited direct effects on both tumor cells and T cells. Importantly, treatment with Compound-182 rendered otherwise resistant tumors sensitive to -PD1 therapy. Our findings establish the potential for small molecule inhibitors of PTP1B and PTPN2 to enhance anti-tumor immunity and combat cancer.

cancer biology↗