tbuckley/cabot-search huggingface dataset:
Photoimmuno‐Lure Nanoplatform for Enhancing T Cell Expansion in Glioblastoma via Synergistic Treatment of Photodynamic Therapy and Immune Checkpoint Inhibition
Authors: Minji Ahn, Yuhyun Na, Hani Choi, Sanghee Lee, Jangsu Lee, Soon A Park, Sin‐Soo Jeun, Kun Na
Journal: Advanced Healthcare Materials (2025)

Abstract The immunosuppressive tumor microenvironment (TME) of glioblastoma (GBM) limits the efficacy of immune checkpoint inhibitors (ICI), primarily due to the absence of cytotoxic T (T c ) cells. In this study, a photoimmuno‐lure nanoplatform is presented that combines amphiphilic photosensitizers (PSs) with Atezolizumab leading to the modulation of the TME of GBM and improvement of the therapeutic efficacy through synergistic photodynamic therapy (PDT). The amphiphilic PSs exhibited four‐fold higher GBM specificity, superior photostability, and enhanced singlet oxygen generation efficiency ( 1 O 2 Φ Δ : 0.92) compared to conventional PSs. In in vitro GBM cell lines, amphiphilic PSs increased immune activation cytokines and improved ICI responsiveness compared to single ICI treatment. In addition, similar results are acquired in a GBM 3D spheroid model, showing significantly elevated T c cell activation. In orthotopic in vivo GBM model, the nanoplatform achieved a 100% survival rate for up to 60 days. Immunological analysis revealed each 2.36‐fold, 4.19‐fold increase in activated dendritic cells and T c cells respectively, and significant reductions in MDSCs (0.48‐fold) and regulatory T cells (0.5‐fold). As a result, this study demonstrates the potential of the synergistic photoimmuno‐lure nanoplatform as a clinical solution to overcome the immunosuppressive TME of GBM and activate innate and adaptive immunity for effective treatment.
Efficacy and safety of CAR T‐cell therapy in patients with primary or secondary CNS lymphoma: A study on behalf of the EBMT and the GoCART coalition
Authors: Anna Ossami Saidy, Christophe Peczynski, Catherine Thieblemont, Michael Daskalakis, Marc Wehrli, David Beauvais, Jürgen Finke, Elisabeth Schorb, Peter Vandenberghe, Philipp Berning, Matthias Stelljes, Francis Ayuk, Ron Ram, Malte Von Bonin, Peter Dreger, Wolfgang Bethge, Andrea Kuhnl, Lasse Jost, Friedrich Stölzel, Bastian von Tresckow, Christoph Renner, Stephan Fuhrmann, Jacques‐Emmanuelle Galimard, Eva Michel, Ali Bazarbachi, Anna Sureda Balari, Norbert Schmitz, Bertram Glass
Journal: HemaSphere (2025)

Abstract Patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary central nervous system (CNS) lymphoma (SCNSL) face a dismal prognosis. They have been excluded from most clinical CAR T‐cell trials as investigators feared an increased risk for severe immune effector cell‐associated neurotoxicity (ICANS). To investigate the potential of anti‐CD19 CAR T‐cell therapy (CART) in such patients, we analyzed data of 100 patients with CNS manifestation treated with CART between January 2018 and July 2023 and reported to European Society for Blood and Marrow Transplantation. Median age was 62 years. Of patients, 58% had failed ≥3 treatment lines, and 40% had received autologous stem‐cell transplantation before CART. Fifty‐nine patients received axicabtagene ciloleucel, 38 patients were treated with tisagenlecleucel, three patients received other products. At the time of CART, 67 patients had active CNS disease. Overall and progression‐free survival (PFS) at 24 months were 37% and 28%. Relapse incidence (RI) at 24 months was 59%, whereas non‐relapse mortality at 1 year was 7%. Cytokine release syndrome (CRS) and ICANS of any grade occurred in 83% and 42% of patients, respectively. CRS grade 3 occurred in 11 and ICANS grades 3–4 in 17 patients. Two patients died of neurotoxicity. Elevated lactate dehydrogenase was an independent risk factor for RI and PFS (hazard ratio [HR] 2.4, p = 0.003; HR: 1.9, p = 0.016). Patients with ECOG 2–3 had a significantly increased risk for the development of ICANS (HR 2.68, p = 0.002). These data support the implementation of CART as treatment for patients with r/r PCNSL and SCNSL.
Intravenous Tenecteplase before Thrombectomy in Stroke
Authors: Zhongming Qiu, Fengli Li, Hongfei Sang, Guangxiong Yuan, Dongjing Xie, Kai Zhou, Maohua Li, Zhaoyou Meng, Zhenyu Kong, Zhongfan Ruan, Chaoqun Li, Guangui Yang, Junxiong Wu, Chen Long, Bo Yang, Hai Hu, Yanling Li, Jun Luo, Zhonghua Shi, Xianjun Huang, Shunfu Jiang, Tingyu Yi, Guoyong Zeng, Jincheng Liu, Xiaojun Luo, Shudong Liu, Mingze Chang, Youlin Wu, Yufeng Tang, Zhenxuan Tian, Zhizhong Yan, Haojin Zhao, Yuqi Peng, Hongguo Dai, Peiyang Zhou, Huagang Li, Wenhua Liu, Dengwen Song, Bo Lei, Zhongbin Xia, Xiaolin Tan, Maojun Zhao, Xinggang Feng, Lingyu Cai, Qi Li, Yuelu Wu, Bingwu Jiang, Yan Tian, Linyu Li, Ling Jiang, Xingmin Long, Feng You, Jian Tao, Jin Zhou, Derong Wu, Chong Zheng, Congguo Yin, Duolao Wang, Mengjie Lu, Gregory W. Albers, Raul G. Nogueira, Bruce C.V. Campbell, Thanh N. Nguyen, Jeffrey L. Saver, Wenjie Zi, Qingwu Yang
Journal: New England Journal of Medicine (2025)

The safety and efficacy of treatment with intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion remain uncertain. In this open-label trial conducted in China, we randomly assigned patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset and were eligible for thrombolysis to receive either intravenous tenecteplase followed by endovascular thrombectomy or endovascular thrombectomy alone. The primary outcome was functional independence (a score of 0 to 2 on the modified Rankin scale; range, 0 to 6, with higher scores indicating more severe disability) at 90 days. Secondary outcomes included successful reperfusion before and after thrombectomy. Safety outcomes included symptomatic intracranial hemorrhage within 48 hours and death within 90 days. A total of 278 patients were randomly assigned to the tenecteplase-thrombectomy group and 272 to the thrombectomy-alone group. Functional independence at 90 days was observed in 147 patients (52.9%) in the tenecteplase-thrombectomy group and in 120 patients (44.1%) in the thrombectomy-alone group (unadjusted risk ratio, 1.20; 95% confidence interval, 1.01 to 1.43; P = 0.04). A total of 6.1% of the patients in the tenecteplase-thrombectomy group and 1.1% of those in the thrombectomy-alone group had successful reperfusion before thrombectomy, and 91.4% and 94.1%, respectively, had successful reperfusion after thrombectomy. Symptomatic intracranial hemorrhage within 48 hours occurred in 8.5% of the patients in the tenecteplase-thrombectomy group and in 6.7% of those in the thrombectomy-alone group; mortality at 90 days was 22.3% and 19.9%, respectively. Among patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset, the percentage of patients with functional independence at 90 days was higher with intravenous tenecteplase plus endovascular thrombectomy than with endovascular thrombectomy alone. (Funded by the Chongqing Science and Health Joint Medical Research Project and others; BRIDGE-TNK ClinicalTrials.gov number, NCT04733742.).
Cholinergic regulation of thymocyte negative selection
Authors: Shaofeng Liu, Chunxing Zheng, Robert Nechanitzky, Ping Luo, Parameswaran Ramachandran, Dat Nguyen, Andrew J Elia, Soode Moghadas Jafari, Rhoda Law, Bryan E Snow, Andrew C Wakeham, Thorsten Berger, Hui Chen, Kyle T Gill, Ryan Mcwilliam, Jerome Fortin, Nastaran Fazel Modares, Mary E Saunders, Kiichi Murakami, Yangmin Qiu, Zhiwei You, Mahmood Mohtashami, Hai Qi, Pamela S Ohashi, Juan Carlos Zúñiga-Pflücker, Tak W Mak
Journal: Nature Immunology (2025)
ACURATE neo2 valve versus commercially available transcatheter heart valves in patients with severe aortic stenosis (ACURATE IDE): a multicentre, randomised, controlled, non-inferiority trial
Authors: Raj R Makkar, Ravi K Ramana, Eric Gnall, Basel Ramlawi, Wen Cheng, Pantelis Diamantouros, Srinivasa Potluri, Neal Kleinman, Aakriti Gupta, Tarun Chakravarty, Sanjay Samy, Andrew Rassi, Vivek Rajagopal, Steven Yakubov, Paul Sorajja, Dhairya Patel, Santiago Garcia, Pradeep Yadav, Vinod Thourani, John Wang, Michael Rinaldi, Samir Kapadia, Ron Waksman, John Webb, Claire Ben Ren, John Gregson, Rodrigo Modolo, Janarthanan Sathananthan, Michael J Reardon
Journal: The Lancet (2025)
Applications of machine learning for immunophenotypic measurable residual disease assessment in acute myeloid leukemia
Authors: Tim R. Mocking, Arjan A. van de Loosdrecht, Jacqueline Cloos, Costa Bachas
Journal: HemaSphere (2025)

Abstract Immunophenotypic detection and quantification of residual leukemic cells by multiparameter flow cytometry is increasingly adopted in the clinical practice of acute myeloid leukemia (AML) to assess measurable residual disease (MRD). However, MRD levels quantified by manual gating analysis can differ based on differences in gating strategy between trained operators and clinical centers. Manual gating requires extensive training, is time‐consuming in daily practice, and faces a significant hurdle in analyzing data from next‐generation cytometry platforms. To address these challenges, several computational approaches involving machine learning and artificial intelligence algorithms have been proposed to automate or aid the assessment of MRD. However, the immunophenotypic variability between patients and the relatively low proportions of residual leukemic cells in AML challenge most algorithms and require innovative approaches. This review provides an overview of recent efforts in using computational methods for immunophenotypic AML‐MRD assessment. We first explain the technical and conceptual background of the different algorithms that have been explored. Next, we discuss their strengths and limitations in the disease‐specific context of AML. Finally, we highlight how computational approaches offer a unique opportunity to standardize or even outperform current manual gating analyses, and ultimately, improve the treatment of AML patients.
Valve Under-Expansion and Clinical Outcomes with ACURATE neo2: Findings from the ACURATE IDE Trial
Authors: Raj R Makkar, Tarun Chakravarty, Aakriti Gupta, Osama Soliman, Eric Gnall, Ravi K Ramana, Basel Ramlawi, Pantelis Diamantouros, Srinivasa Potluri, Neal Kleiman, Sanjay Samy, Andrew Rassi, Pradeep Yadav, Vinod Thourani, Steven Yakubov, Chris Frawley, Dhairya Patel, Samir Kapadia, Aaron Chalekian, Rodrigo Modolo, Janarthanan Sathananthan, Won-Keun Kim, Michael J Reardon
Journal: Journal of the American College of Cardiology (2025)
Genomic landscape of multiple myeloma and its precursor conditions
Authors: Jean-Baptiste Alberge, Ankit K Dutta, Andrea Poletti, Tim H H Coorens, Elizabeth D Lightbody, Rosa Toenges, Xavi Loinaz, Sofia Wallin, Andrew Dunford, Oliver Priebe, Johnathan Dagan, Cody J Boehner, Erica Horowitz, Nang K Su, Hadley Barr, Laura Hevenor, Katherine Towle, Rashmika Beesam, Jenna B Beckwith, Jacqueline Perry, David M Cordas Dos Santos, Luca Bertamini, Patricia T Greipp, Kirsten Kübler, Peter F Arndt, Carolina Terragna, Elena Zamagni, Eileen M Boyle, Kwee Yong, Gareth Morgan, Brian A Walker, Meletios Athanasios Dimopoulos, Efstathios Kastritis, Julian Hess, Romanos Sklavenitis-Pistofidis, Chip Stewart, Gad Getz, Irene M Ghobrial
Journal: Nature Genetics (2025)

Reliable strategies to capture patients at risk of progression from precursor stages of multiple myeloma (MM) to overt disease are still missing. We assembled a comprehensive collection of MM genomic data comprising 1,030 patients (218 with precursor conditions) that we used to identify recurrent coding and non-coding candidate drivers as well as significant hotspots of structural variation. We used those drivers to define and validate a simple 'MM-like' score, which we could use to place patients' tumors on a gradual axis of progression toward active disease. Our MM precursor genomic map provides insights into the time of initiation and cell-of-origin of the disease, order of acquisition of genomic alterations and mutational processes found across the stages of transformation. Taken together, we highlight here the potential of genome sequencing to better inform risk assessment and monitoring of MM precursor conditions.
Bat organoids reveal antiviral responses at epithelial surfaces
Authors: Max J Kellner, Vanessa M Monteil, Patrick Zelger, Gang Pei, Jie Jiao, Masahiro Onji, Komal Nayak, Matthias Zilbauer, Anne Balkema-Buschmann, Anca Dorhoi, Ali Mirazimi, Josef M Penninger
Journal: Nature Immunology (2025)

Abstract Bats can host viruses of pandemic concern without developing disease. The mechanisms underlying their exceptional resilience to viral infections are largely unresolved, necessitating the development of physiologically relevant and genetically tractable research models. Here, we developed respiratory and intestinal organoids that recapitulated the cellular diversity of the in vivo epithelium present in Rousettus aegyptiacus , the natural reservoir for the highly pathogenic Marburg virus (MARV). In contrast to human counterparts, bat organoids and mucosal tissue exhibited elevated constitutive expression of innate immune effectors, including type I interferon-ε (IFNε) and IFN-stimulated genes (ISGs). Upon infection with diverse zoonotic viruses, including MARV, bat organoids strongly induced type I and III IFN responses, which conferred robust antiviral protection. Type III IFNλ3 additionally displayed virus-independent self-amplification, acting as an ISG to enhance antiviral immunity. Our organoid platform reveals key features of bat epithelial antiviral immunity that may inform therapeutic strategies for viral disease resilience.
A single-cell spatial chart of the airway wall reveals proinflammatory cellular ecosystems and their interactions in health and asthma
Authors: Régis Joulia, Sara Patti, William J Traves, Lola Loewenthal, Laura Yates, Simone A Walker, Franz Puttur, May Al-Sahaf, Katherine N Cahill, Juying Lai, Salman Siddiqui, Joshua A Boyce, Elliot Israel, Clare M Lloyd
Journal: Nature Immunology (2025)

Abstract Determining spatial location of cells within tissues gives vital insight into the interactions between resident and inflammatory cells and is a critical factor for uncoupling the mechanisms driving disease. Here, we apply single-cell spatial transcriptomics to reveal the airway wall landscape in health and during asthma. We identified proinflammatory cellular ecosystems that exist within discrete spatial niches in healthy and asthma samples. These cellular hubs are characterized by a high level of chemokine and alarmin expression, along with unique combinations of stromal cells. Mechanistically, we demonstrated that receptors, such as ACKR1, retain immune mediators locally, while amphiregulin-expressing mast cells are prominent within these proinflammatory hubs. Despite anti-inflammatory treatments, the asthma airway mucosa exhibited a distinct remodeling program within these cellular ecosystems, marked by increased proximity between key cell types. This study provides an unprecedented view of the topography of the airway wall, revealing distinct, specific ecosystems within spatial niches to target for therapeutic intervention.
Intracellular L-PGDS–Derived 15d-PGJ2 Inhibits CaMKII Through Lipoxidation to Alleviate Cardiac Ischemia/Reperfusion Injury
Authors: Qingmei Hu, Junxia Zhang, Xile Luo, Peiyu Hu, Jiayi Li, Fan Li, Zeyuan Wang, Shuyang Zhang, Zishan Jiao, Yitong Liu, Jiaxin Duanmu, Li Jin, Peng Xie, Wenneng Zhu, Wen Zheng, Haibao Shang, Xinli Hu, Zhixing Chen, Rui-Ping Xiao, Yan Zhang
Journal: Circulation (2025)

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is a substantial challenge to the management of ischemic heart disease, the leading cause of mortality worldwide. Arachidonic acid (AA) is a prominent polyunsaturated fatty acid in the human body and plays an important role in various physiological and pathological conditions. AA metabolic enzymes determine AA levels; however, currently there is no comprehensive analysis of AA enzymes in cardiac I/R injury. METHODS: The profiling of AA metabolic enzymes was analyzed with the RNA sequencing transcriptome data from the mouse heart tissues with I/R injury. Cultured neonatal and adult rat ventricular myocytes, human embryonic stem cell–derived cardiomyocytes, and in vivo mouse I/R models were used to confirm the role of L-PGDS (lipocalin-type prostaglandin D2 synthase)/15d-PGJ2 in I/R injury. A biotin-tagged 15d-PGJ2 analog combined with liquid chromatography–tandem mass spectrometry was used to identify the downstream signaling of L-PGDS/15d-PGJ2. RESULTS: Based on the transcriptome data and experimental validations, L-PGDS, together with its downstream metabolite 15d-PGJ2, was downregulated in cardiac tissue with I/R injury. Functionally, L-PGDS overexpression mitigates myocardial I/R injury, whereas knockdown exacerbates the damage. Supplementation of 15d-PGJ2 alleviated I/R injury. Mechanistically, 15d-PGJ2 covalently bound to the Ca 2+ /CaMKII (calmodulin protein kinase II) and induced lipoxidation of its cysteine 495 (CaMKII-δ9) to dampen the formation of CaMKII oligomers and alleviate its overactivation, consequently ameliorating cardiomyocyte death and cardiac injury. CONCLUSIONS: Our study uncovered L-PGDS/15d-PGJ2/CaMKII signaling as a new mechanism underlying I/R-induced cardiomyocyte death. This provides new mechanistic insights and therapeutic targets for myocardial I/R injury and subsequent heart failure. We also showed that lipoxidation is a new post-translational modification type for CaMKII, deepening our understanding of the regulation of its activity.
Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy
Authors: Ting Wen, Yanping Fu, Xiangting Yi, Ying Sun, Wanchen Zhao, Chaonan Shi, Ziyao Chang, Beibei Yang, Shuling Li, Chao Lu, Tingting Peng, Chuanbin Wu, Xin Pan, Guilan Quan
Journal: Acta Pharmaceutica Sinica B (2025)
Age-stratified associations between radiotherapy and SPMs for FPHNC: a population-based cohort study
Authors: Yuan-Yuan Li, Qiong Liu, Si-Qi Ying, Xiu-Quan Wu, Xiao-Hui Zhang, Xiao-Mei Xie, Bing-Dong Sui, Yan Jin, Yang Jiao, Franklin R Tay
Journal: Military Medical Research (2025)

Abstract Background Second primary malignancies (SPMs) account for over 30% of total deaths in head and neck cancer (HNC) patients. The increasing use of radiotherapy raises concerns about the elevated risk of radiation-associated SPMs. This study aimed to investigate the age-stratified association between radiotherapy and SPM risk in survivors of non-metastatic primary HNC. Methods Using data from the Surveillance, Epidemiology, and End Results program (2004−2015), incidence rate ratios (IRRs) and standardized incidence ratios (SIRs) were evaluated for solid and hematologic SPMs associated with radiotherapy within different age groups. Follow-up for hematologic and solid SPMs began 2 and 5 years, respectively, after the diagnosis of first primary HNC. The IRRs for SPMs were compared between radiotherapy-exposed and unexposed groups using multivariable modified Poisson regression. The SIRs were computed as the ratio of observed cancers in the cohort to expected cases derived from sex-, age-, and calendar year-matched general population incidence rates. Results The study included 75,209 2-year survivors, with 73.2% being male and a median age of 60 years. Of these, 58,063 had survived 5 years or more. Radiotherapy was associated with an increased risk of solid SPMs [IRR = 1.16, 95% confidence interval (CI) 1.08−1.24; P &lt; 0.001]. The associations varied significantly among young (aged 15−39 years), middle-aged (aged 40 − 64 years), and elderly (aged 65−89 years) patients. Specifically, radiotherapy was associated with an increased risk of solid SPMs in middle-aged patients (IRR = 1.21, 95% CI 1.11−1.32; P &lt; 0.001), and a decreased risk of hematologic SPMs in elderly patients (IRR = 0.77, 95% CI 0.60−0.99; P = 0.045). Compared with the general population, young patients had an elevated risk of radiotherapy-associated second primary non-Hodgkin lymphoma (SIR = 4.01, 95% CI 1.47−8.74). Middle-aged patients showed the highest SIR for SPMs in the bones/joints (SIR = 7.72, 95% CI 4.32−12.73), while elderly patients had the highest SIR for second primary esophageal malignancies (SIR = 3.87, 95% CI 2.91−5.05). Males were more likely to develop solid SPMs compared to females. Conclusions This study reveals an age-stratified association between radiotherapy and the risk of SPMs in HNC patients. These findings highlight the importance of considering patient age when making treatment decisions for HNC and suggest that long-term surveillance is necessary for high-risk groups.
Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease
Authors: Haiyuan Shen, Suthat Liangpunsakul, Yasuko Iwakiri, Gyongyi Szabo, Hua Wang
Journal: Cellular and Molecular Immunology (2025)

Abstract Alcohol-associated liver disease (ALD) is a major global health challenge, with inflammation playing a central role in its progression. As inflammation emerges as a critical therapeutic target, ongoing research aims to unravel its underlying mechanisms. This review explores the immunological pathways of ALD, highlighting the roles of immune cells and their inflammatory mediators in disease onset and progression. We also examine the complex interactions between inflammatory cells and non-parenchymal liver cells, as well as their crosstalk with extra-hepatic organs, including the gut, adipose tissue, and nervous system. Furthermore, we summarize current clinical research on anti-inflammatory therapies and discuss promising therapeutic targets. Given the heterogeneity of ALD-associated inflammation, we emphasize the need for precision medicine to optimize treatment strategies and improve patient outcomes.
Brain tumors induce immunoregulatory dendritic cells in draining lymph nodes that can be targeted by OX40 agonist treatment
Authors: Oscar Badillo-Godinez, Jenni Niemi, Liam Helfridsson, Shokoufeh Karimi, Mohanraj Ramachandran, Hitesh Bhagavanbhai Mangukiya, Sven Nelander, Mats Hellström
Journal: Journal for ImmunoTherapy of Cancer (2025)

Primary and metastatic brain tumors have a poor prognosis, partly owing to the unique characteristics of the central nervous system (CNS) and tumor immune microenvironment (TIME). One distinct feature of the CNS TIME is the limited infiltration and activation of dendritic cells (DCs). The impact of CNS versus non-CNS TIME can be assessed by injecting tumor cells from the same model, either subcutaneously (peripherally) or into the brain. Subcutaneous tumors drain into the tumor-draining lymph nodes in the skin (TdLN-p), whereas brain tumors drain into the deep cervical TdLN (TdLN-c). We previously showed that CNS tumors that are not responsive to immune checkpoint inhibition become responsive when grown peripherally, and that non-responsiveness correlates with a tolerogenic immune response in the local TIME and TdLN-c. In this study, we investigated the immunoregulatory potential of cervical DCs (DC-c) compared with that of peripheral DCs (DC-p) using high-resolution flow cytometry, single-cell RNA sequencing, and ex vivo and in vivo functional characterization of TdLNs from mouse models of glioma and lymphoma. Our analysis revealed that DC-c promoted regulatory T-cell expansion and poorly cytotoxic CD8+ T cells compared with DC-p. Furthermore, we identified OX40 (Tnfrsf4) as a modulator of immunoregulatory DC-c function and found that its antitumor effect depended on lymphocyte trafficking and the DC transcription factor Batf3. CCR7+OX40+ DCs were efficient in antigen processing and presentation, and OX40 agonists further enhanced DC activation. In TIME, the CCR7+OX40+ DCs expressed OX40L, and blocking it promoted Treg formation ex vivo. Our findings highlight the unique immunoregulatory functions of DC-c in TdLNs and suggest the importance of OX40 signaling through direct effects on CCR7+OX40+ DCs and indirect effects on T cells.