tbuckley/cabot-search huggingface dataset:
Single-cell RNA sequencing of human double-negative T cells reveals a favorable cellular signature for cancer therapy
Authors: Enoch Tin, Ismat Khatri, Karen Fang, Yoosu Na, Michele Nawata, Juan Arteaga, Mark D Minden, Sergio Rutella, Jongbok Lee, Li Zhang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Allogeneic double-negative T-cell (DNT) therapy has emerged as a novel, off-the-shelf cellular treatment with clinical feasibility, safety, and promising efficacy against leukemia. However, the biology of DNTs is less well characterized, and how DNT therapy distinguishes from conventional γδ T-cell therapy remains unclear. Collectively, this hinders our ability to bolster DNT functionalities in cancer therapy. Here, we performed single-cell RNA sequencing with in vitro and in vivo functional analysis on DNTs. As a significant proportion of DNTs express Vγ9Vδ2 (Vδ2) TCR chain, we compared DNTs with donor-matched conventional Vδ2 T cells expanded with zoledronic acid. Methods Healthy donor-derived allogeneic DNTs and Vδ2 T cells were expanded ex vivo. Single-cell RNA sequencing analysis was performed on both cellular products to identify the transcriptional landscape and inferred cellular interactions within DNTs, followed by comparisons with donor-matched Vδ2 T cells. Unique cellular subsets found only in DNTs were depleted to identify their contributions to the overall efficacy of DNTs against acute myeloid leukemia. The anti-leukemic activity and in vivo persistence of DNTs and Vδ2 T-cells were explored using flow cytometry-based cytotoxicity assays, memory phenotyping, and xenograft models. Results Despite a shared Vδ2 expression between cellular products, we identified unique cellular compositions in DNTs that contribute to distinct transcriptional and cellular communication patterns relative to the donor-matched Vδ2 T cells, including higher expression of genes identified in chimeric antigen receptor T cells that persist in patients with durable cancer-remission. Vδ2 – DNTs exhibited strong persistence characteristics, and their presence promoted the cytotoxic capabilities of Vδ2 + DNTs in repeated stimulation assays. This unique genetic signature and diverse cellular composition of DNTs resulted in better overall ex vivo expansion, prolonged persistence, and superior anti-leukemic activity compared with Vδ2 T cells in vitro and in vivo. Conclusions These results highlight the unique transcriptional, cellular, and functional profile of human DNTs and support the continued clinical investigation of allogeneic DNT therapy. The data also provide a reference gene signature that may help improve the efficacy of other types of allogeneic adoptive cellular therapies.
Past failures and new horizons: the nuances of tertiary lymphoid structures in high-grade serous ovarian cancer may contribute to immunotherapy effectiveness
Authors: Rufiaat Rashid, Lan Coffman, Tullia C Bruno, Ian MacFawn
Journal: Journal for ImmunoTherapy of Cancer (2025)

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that allow for optimal B-T cell crosstalk in solid tumors. Further, TLS are found in many solid tumors and are associated with improved patient survival and superior immunotherapeutic response, ultimately reflecting their potential as new therapeutic targets. Despite the prognostic benefit of TLS, women with high-grade serous ovarian cancer (HGSOC) are insensitive to immunotherapies. We have summarized recent work on TLS in patients with HGSOC, ultimately demonstrating how tumor microenvironment factors and therapeutics shape the organization and maturation of TLS. Specifically, TLS function varies across anatomical sites, with more germinal center (GC)+TLS with active B cells found in tumors within the omentum and fallopian tube compared with ovary. Further, cancer-associated stromal cells within patients negate the prognostic benefit of TLS and reduce B cell recruitment and function with blunted differentiation of follicular dendritic cells, which lay the foundation for functional GCs. Neoadjuvant chemotherapy (NACT) also impacts the HGSOC microenvironment, with metastatic tumors showing increased infiltration of effector immune cells (primarily TCF1+PD1+ CD8+ T cells) and “mature” TLS formation compared with NACT-naïve patients. These findings provide a rationale for designing therapeutics targeting the HGSOC TLS landscape and restoring immunotherapeutic responses in these patients.
Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition
Authors: Joseph G Matous, Jeremy P Snook, Nico A Contreras, Andrew G Ramstead, Krystal R Charley, Elizabeth M Kolawole, Jacob N Kisiolek, Kaitlyn A Flint, Ashleigh J Soedel, Breyana Robinson, Anaiya B Mendoza, Yohichi Kumaki, Brian D Evavold, Matthew A Williams
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background The presence of activated CD8 T cells in the tumor microenvironment is correlated with an effective immune response to immune checkpoint inhibitor (ICI) therapy. However, ICI predominantly targets high-affinity T cells, which may be less abundant in tumors with few neoantigens. Targeting the intracellular phosphatase Src homology region 2 domain-containing phosphatase-1 (Shp-1) in combination with ICI lowers the T cell activation threshold and enhances the ability of low-affinity T cells to mount a productive antitumor response. Methods In this study, we sought to determine whether temporal inhibition of Shp-1 during active tumor growth could rescue the activity of low-affinity T cells specific for endogenous self-antigens. To address this question, we implanted Yale University Mouse Melanoma (YUMM) tumor cell lines into WT mice and, on tumor establishment, administered an inhibitor of Shp-1 (TPI-1) with or without ICI treatment. We analyzed treatment-dependent changes in the immune infiltrate in the tumor via flow cytometry, major histocompatibility complex (MHC) tetramer-mediated detection of tyrosinase-related protein 2 (TRP-2) 180–188 -specific T cells and a micropipette-based two-dimensional affinity assay to measure the T cell receptor (TCR) affinity. Results Administration of ICI and a Shp-1 inhibitor to mice with established YUMM tumors, but neither agent alone, resulted in a significant delay in tumor growth and an increased frequency of CD8 tumor-infiltrating T cells with enhanced effector and reduced exhaustion characteristics. In particular, combined treatment increased the frequency of CD8 T cells specific for the MHC Class I-restricted tumor self-antigen TRP-2 180–188 . We found that the increase in effector T cells was almost entirely due to an increase in T cells with very low TCR affinity. Conclusions We conclude that approaches for altering TCR signaling threshold are effective in enhancing the antitumor response of low-affinity T cells specific for endogenous self-antigens in settings of ICI resistance and/or where neoantigens are not available to drive antitumor responses.
LILRB2 blockade facilitates macrophage repolarization and enhances T cell-mediated antitumor immunity
Authors: Des C Jones, Lorraine Irving, Rebecca Dudley, Seraina Blümli, Marcin Wolny, Elisavet I Chatzopoulou, Stacy Pryts, Shreya Ahuja, D Gareth Rees, Alan M Sandercock, Saravanan Rajan, Reena Varkey, Michael Kierny, Andrew Kayserian, Kathy Mulgrew, Georgina Bowyer, Saly Songvilay, Kamila Bienkowska, Matthew S Glover, Sonja Hess, Simon J Dovedi, Robert W Wilkinson, Fernanda Arnaldez, Mark Cobbold
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors have revolutionized the treatment of solid tumors, enhancing clinical outcomes by releasing T cells from inhibitory effects of receptors like programmed cell death protein 1 (PD-1). Despite these advancements, achieving durable antitumor responses remains challenging, often due to additional immunosuppressive mechanisms within the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) contribute significantly to the immunosuppressive TME and play a pivotal role in shaping T cell-mediated antitumor responses. Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2), expressed on myeloid cells, including TAMs, is an inhibitory receptor, which contributes to macrophage-mediated immunosuppression. In this study, we present AZD2796, a high-affinity anti-LILRB2 antibody designed to repolarize TAMs from an immunosuppressive to a proinflammatory phenotype. Methods Anti-LILRB2 antibodies were identified using single-B-cell encapsulation Immune Replica technology. The ability of AZD2796 to enhance proinflammatory responses from macrophages treated with CD40 ligand or lipopolysaccharide was assessed using a macrophage stimulation assay. A tumor cell/macrophage/T cell co-culture assay was developed to evaluate the effect of AZD2796, as a single agent and in combination with an anti-PD-1 antibody, on the cytolytic activity of antigen-specific T cells. In vivo assessments were then carried out to determine the ability of AZD2796 to alter tumor growth rate in mice humanized with CD34 hematopoietic stem cells. Results In preclinical assessments, AZD2796 skewed macrophage differentiation away from an immunosuppressive phenotype and enhanced the proinflammatory function of macrophages. AZD2796 significantly increased the anti-tumor response of T cells following PD-1 checkpoint blockade, while AZD2796 monotherapy reduced tumor growth in humanized mouse models. Conclusions These findings support the potential of AZD2796 as an anti-cancer therapy, with the ability to synergize with T-cell-based therapeutics.
Pediatric Arsenical Keratosis
Authors: Xu Li, Lili Zhi
Journal: British Journal of Dermatology (2025)

We report a rare case of pediatric arsenical keratosis in an 8-year-old girl presenting with chronic hyperkeratotic lesions and mottled pigmentation, linked to an unidentified oral medication. Elevated blood arsenic levels and histopathological features confirmed the diagnosis. The case highlights the importance of exposure history and long-term dermatologic surveillance in children with atypical keratotic dermatoses.
Patient Centric Performance and Interpretation of SPECT and SPECT/CT Myocardial Perfusion Imaging. A Clinical Consensus Statement of the European Association of Cardiovascular Imaging of the ESC
Authors: Bryan Abadie, Riccardo Liga, Ronny Buechel, Andreas A Giannopoulos, María Nazarena Pizzi, Albert Roque, Ricardo Geronazzo, Fabien Hyafil, Juhani Knuuti, Antti Saraste, Riemer Slart, Paul Cremer, Richard Weinberg, Maria João Vidigal Ferreira, Alessia Gimelli, Wael Jaber
Journal:  (2025)

Abstract The non-invasive assessment of ischaemic heart disease with myocardial perfusion imaging remains an integral part of modern cardiology. This modality has been used for decades, but improving technology has maintained its relevance today. This document describes the fundamentals of single-photon emission computed tomography, including stress protocols, tracer pharmacodynamics, camera settings and capabilities, post-acquisition processing, and clinical translation in an easy to read and highly pictorial manner to be applicable to not only healthcare providers of all levels, but patients as well.
Reduced insulin use and diabetes complications upon introduction of SGLT-2 inhibitors and GLP1-receptor agonists in low- and middle-income countries: A microsimulation
Journal: PLoS Medicine (2025)

Background Diabetes mellitus, particularly type 2 diabetes, is a growing health concern in low- and middle-income countries (LMICs). The potential impact of newer diabetes medications, such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, on insulin dosage and health outcomes in these settings is not well understood. Methods and findings We developed a microsimulation model to estimate the impact of treating patients with type 2 diabetes who use insulin with GLP-1 receptor agonists or SGLT-2 inhibitors in LMICs. The model utilized data from the Global Health and Population Project on Access to Care for Cardiometabolic Diseases (HPACC) dataset, encompassing surveys from 79 countries and clinical trial data to estimate insulin dose reduction. We incorporated weight-based insulin dosing formulas and hazard ratios for severe hypoglycemia, cardiovascular and renal outcomes, side effects of new therapies, and mortality. The primary outcome was the change in insulin dosage, and secondary outcomes were disability-adjusted life years (DALYs) lost per 1,000 person-years by diabetes complication (micro- and macro-vascular). Our results indicate that the addition of GLP-1 receptor agonists or SGLT-2 inhibitors could reduce insulin dosage by 8.2 IU/day (IQR: 6.9, 9.5) and 5.3 IU/day (IQR: 4.5, 6.2), respectively. The median DALYs lost per 1,000 person-years decreased from 2.20 (IQR: 1.49, 4.02) to 1.01 (IQR: 0.61, 1.86) with GLP-1 receptor agonists and 1.25 (IQR: 0.81, 2.29) with SGLT-2 inhibitors. Primary benefits arose from weight loss, decreased cardiorenal disease, and decreased mortality, with smaller DALY benefits from the prevention of severe hypoglycemia. Key limitations include the inability to differentiate between type 1 and type 2 diabetes in some datasets and reliance on assumptions from clinical trials conducted primarily in high-income countries. Conclusions The introduction of GLP-1 receptor agonists and SGLT-2 inhibitors for managing type 2 diabetes in LMICs could significantly reduce insulin dosage and associated health risks, leading to improved outcomes and reduced disability. These findings suggest that expanding access to these newer diabetes medications in LMICs could have substantial public health benefits.
Correction: Comparing cervical cerclage, pessary and vaginal progesterone for prevention of preterm birth in women with a short cervix (SuPPoRT): A multicentre randomised controlled trial
Authors: Natasha L. Hezelgrave, Natalie Suff, Paul Seed, Vicky Robinson, Jenny Carter, Helena Watson, Alexandra Ridout, Anna L. David, Susana Pereira, Fatemeh Hoveyda, Joanna Girling, Latha Vinayakarao, Rachel M. Tribe, Andrew H. Shennan
Journal: PLoS Medicine (2025)

[This corrects the article DOI: 10.1371/journal.pmed.1004427.].
BCMA-CAR T-cells in a patient with relapsing idiopathic inflammatory myositis after CD19-CAR T-cells
Authors: Fabian Müller, Andreas Wirsching, Melanie Hagen, Simon Völkl, Carlo Tur, Maria Gabriella Raimondo, Jule Taubmann, Laura Bucci, Liang Zhang, Sascha Kretschmann, Michael Aigner, Markus Eckstein, Silvia Spörl, Soraya Kharboutli, Sebastian Böltz, Armin Atzinger, Luis Munoz, Georg Schett, Andreas Mackensen, Ricardo Grieshaber-Bouyer
Journal: Nature Medicine (2025)
Pleural fluid proteomics from patients with pleural infection shows signatures of diverse neutrophilic responses: The Oxford Pleural Infection Endotyping Study (TORPIDS-2)
Authors: Nikolaos I Kanellakis, Elie Antoun, Kiki Cano-Gamez, Julia Chu, Nikita Manoharan, Georgina Berridge, Iolanda Vendrell, Zheqing Zhang, John P Corcoran, Alguili Elsheikh, Tao Dong, Roman Fischer, Justin P Whalley, Julian C Knight, Najib M Rahman
Journal: European Respiratory Journal (2025)

Background Pleural infection is a complex disease with poor clinical outcomes and increasing incidence worldwide, yet its biological endotypes remain unknown. Methods We analysed 80 pleural fluid samples from the PILOT study, a prospective study on pleural infection, using unlabelled mass spectrometry. A total of 449 proteins were retained after filtering. Unsupervised hierarchical clustering and UMAP analyses were used to cluster samples and pathway analysis was performed to identify the biological processes. Protein signatures as identified by the pathway analysis were compared to microbiology as defined by 16S rRNA next generation sequencing. Spearman and exact Fischer's methods were used for correlation assessment. Results Higher neutrophil degranulation was correlated with increased glycolysis (OR=281, p&lt;2.2E−16) and pentose phosphate activation (OR=371.45, p&lt;2.2E−16). Samples dominated by Streptococcus pneumoniae exhibited higher neutrophil degranulation (OR=12.08, p=0.005), glycolysis (OR=11.4, p=0.006), and pentose phosphate activity (OR=12.82, p=0.004). On the other hand, samples dominated by anaerobes and Gram-negative bacteria exhibited lower neutrophil degranulation (OR=0.15, p=0.01, glycolysis (OR=0.14, p=0.01), and pentose phosphate activity (OR=0.07, p=0.001). Increased activity of the liver and retinoid X receptors (LXR-RXR) pathway was associated with lower risk of one-year mortality (OR=0.24, p=0.04). Conclusions These findings suggest that pleural infection patients exhibit diverse responses of neutrophil mediated immunity, glycolysis, and pentose phosphate activation which are associated with microbiology. Therapeutic targeting of the LXR-RXR pathway with agonists is a possible treatment approach.
Spironolactone inhibits the NLRP1 inflammasome and alleviates defective erythropoiesis in Diamond‐Blackfan anemia
Authors: Lola Rodríguez‐Ruiz, Juan M. Lozano‐Gil, María Ocaña‐Esparza, Ana M. Conesa‐Hernández, Ana B. Pérez‐Oliva, José L. Fuster, Andrés Jérez, Laura Murillo‐Sanjuán, Cristina Díaz‐de‐Heredia, Guzmán López‐de‐Hontanar, Julián Sevilla, Diana García‐Moreno, María L. Cayuela, Alicia Martínez‐López, Sylwia D. Tyrkalska, Victoriano Mulero
Journal: HemaSphere (2025)
A German multicenter real‐world analysis of talquetamab in 138 patients with relapsed/refractory multiple myeloma
Authors: Jan H. Frenking, Christine Riedhammer, Raphael Teipel, Florian Bassermann, Britta Besemer, Moritz Bewarder, Jan Braune, Annamaria Brioli, Franziska Brunner, Maria Dampmann, Roland Fenk, Deniz N. Gezer, Sarah Goldman‐Mazur, Christine Hanoun, Marion Högner, Cyrus Khandanpour, Katja Kolditz, Igor Kos, Jan Krönke, Miriam Kull, Valentine Landrin, Theo Leitner, Maximilian Merz, Ivana von Metzler, Christian S. Michel, Carsten Müller‐Tidow, Sebastian Theurich, Karolin Trautmann‐Grill, Ralph Wäsch, Romans Zukovs, Mathias Hänel, Leo Rasche, Marc S. Raab
Journal: HemaSphere (2025)

Abstract Bispecific T‐cell engagers (BTCEs) represent a paradigm shift in the treatment of relapsed/refractory multiple myeloma (RRMM). Talquetamab, a GPRC5DxCD3 BTCE, has shown promising results in the MonumenTAL‐1 trial and was recently approved by the Food and Drug Administration and the European Medicines Agency. However, treatment under real‐world conditions may not represent patient characteristics in clinical trials with restricted enrollment criteria. We performed a retrospective real‐world analysis including 138 RRMM patients treated with talquetamab at 21 German centers. Of evaluable patients, 43% had ISS stage III, 37% had extraosseous disease, and 48% had high‐risk cytogenetics. After a median of six prior therapy lines, 58% of patients would not have been eligible for MonumenTAL‐1. With a median follow‐up of 8.2 months, we observed an overall response rate of 65% and a median progression‐free survival of 6.4 months (95% confidence interval 5.1–9.0). Prior BTCE exposure, ISS stage III, extraosseous disease, and penta‐drug refractory disease were associated with unfavorable outcomes. Grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 5.1% and 1.5% of patients, respectively. In summary, our real‐world study confirms the efficacy and safety of talquetamab, despite a high proportion of patient‐ and disease‐related risk factors. These results support its use as bridging or long‐term treatment, even in advanced stages.
Lymphovascular invasion is an independent predictor of metastasis and disease-specific death in cutaneous squamous cell carcinoma: a multicenter retrospective study
Authors: Kelsey E Hirotsu, Sumaira Z Aasi, Kaeli K Samson, Cheng Zheng, Jaron R Nazaroff, Lindsey M Voller, Emily S Ruiz, Nina A Ran, Emily E Granger, Shlomo A Koyfman, Allison T Vidimos, David R Carr, Kathryn T Shahwan, John A Carucci, Joi B Carter, Javier Cañueto, Fábio Muradás Girardi, Aaron R Mangold, Divya Srivastava, David G Brodland, John A Zitelli, Tyler J Willenbrink, Ashley Wysong
Journal: Journal of the American Academy of Dermatology (2025)
Prevalence of Obesity With and Without Confirmation of Excess Adiposity Among US Adults
Authors: Ebenezer K. Aryee, Sui Zhang, Elizabeth Selvin, Michael Fang
Journal: JAMA (2025)

This study compares the prevalence of obesity (assessed by body mass index only) vs obesity prevalence when excess adiposity is confirmed by waist circumference measurement or dual-energy x-ray absorptiometry in a nationally representative sample of US adults.
Intravenous Iron–Induced Hypophosphatemia in Surgical Patients
Authors: Toby Richards, Linda K. Wijaya, Jayne Lim, Cory Dugan, Darren Dahly
Journal: JAMA Network Open (2025)

This study explores the incidence of preoperative hypophosphatemia and whether hypophosphatemia may have affected patient or trial outcomes for those who received ferric carboxymaltose.
COVID-19 Pandemic–Related Exposures and Cognitive Function in Middle-Aged Women
Authors: Siwen Wang, Anthony Menor, Lori B. Chibnik, Jae H. Kang, Chirag M. Vyas, Deborah L. Blacker, Laura D. Kubzansky, Karestan C. Koenen, Andrea L. Roberts
Journal: JAMA Network Open (2025)

Importance The COVID-19 pandemic has been associated with risk factors for cognitive decline, such as bereavement and SARS-CoV-2 infection. Objective To examine whether the COVID-19 pandemic and pandemic-related exposures are associated with cognitive function among middle-aged women. Design, Setting, and Participants This cohort study analyzed data from the Nurses’ Health Study II, an ongoing study of registered nurses in the US. The present study focused on women aged 51 to 76 years who completed 2 to 8 objective cognitive assessments both prior to (October 1, 2014, to February 29, 2020) and during the COVID-19 pandemic (March 1, 2020, to September 30, 2022). Statistical analyses were performed from January 2023 to January 2025. Exposure COVID-19 pandemic. Main Outcomes and Measures Two standardized (ie, z -scored) composite cognitive scores (psychomotor speed and attention, learning and working memory) and a global score constituted the primary outcomes. Higher scores indicated better cognitive function. Cognitive function was assessed using the Cogstate Brief Battery, a computer-administered cognitive test battery. Participants completed cognitive assessments every 6 to 12 months. Results A total of 5191 women (mean [SD] age at first cognitive assessment, 63.0 [4.8] years) completed both prepandemic and during-pandemic measures, contributing 23 678 cognitive assessments. After adjustment for age at cognitive assessment, educational level for both participants and their parents, cognitive test practice effects, and comorbidities (eg, diabetes, hypertension), no difference in cognitive function was observed between assessments taken during vs before the pandemic (psychomotor speed and attention: β = −0.01 SD [95% CI, −0.05 to 0.02 SD]; learning and working memory: β = 0.00 SD [95% CI, −0.03 to 0.03 SD]; global score: β = 0.00 SD [95% CI, −0.03 to 0.02 SD]). Among 4456 participants who responded to the COVID-19 substudy (ie, surveys about pandemic-related events), those with a history of SARS-CoV-2 infection (164 [3.7%]) or post–COVID-19 conditions (PCC; 62 [1.4%]), at a median (IQR) 20.0 (18.5-22.1) months after initial infection, had reduced cognitive function compared with women without infection or PCC; however, these differences did not reach statistical significance, and the wide CIs suggested considerable uncertainty. Conclusions and Relevance This cohort study of middle-aged women found that the COVID-19 pandemic and pandemic-related events were not associated with cognitive decline up to 2.5 years after the onset of the pandemic. Future studies are needed to examine the long-term implications of SARS-CoV-2 infection and PCC for cognitive function.