tbuckley/cabot-search huggingface dataset:
Combating cancer immunotherapy resistance: a nano‐medicine perspective
Authors: Xiangyi Kong, Xintong Xie, Juan Wu, Xiangyu Wang, Wenxiang Zhang, Shuowen Wang, Daria Valerievna Abbasova, Yi Fang, Hongnan Jiang, Jidong Gao, Jing Wang
Journal: Cancer Communications (2025)

Abstract Cancer immunotherapy offers renewed hope for treating this disease. However, cancer cells possess inherent mechanisms that enable them to circumvent each stage of the immune cycle, thereby evading anti‐cancer immunity and leading to resistance. Various functionalized nanoparticles (NPs), modified with cationic lipids, pH‐sensitive compounds, or photosensitizers, exhibit unique physicochemical properties that facilitate the targeted delivery of therapeutic agents to cancer cells or the tumor microenvironment (TME). These NPs are engineered to modify immune activity. The crucial signal transduction pathways and mechanisms by which functionalized NPs counteract immunotherapy resistance are outlined, including enhancing antigen presentation, boosting the activation and infiltration of tumor‐specific immune cells, inducing immunogenic cell death, and counteracting immunosuppressive conditions in the TME. Additionally, this review summarizes current clinical trials involving NP‐based immunotherapy. Ultimately, it highlights the potential of nanotechnology to advance cancer immunotherapy.
Dissolving Microneedles Embedded with Photosensitizers for Targeted Eradication of Gram‐Positive Bacteria in Multidrug‐Resistant Biofilms in Diabetic Wound Infections
Authors: Ruyan Xie, Duoyang Fan, Yanpeng Fang, Tianyu Zhu, Haohan Li, Ying Yin, Xiaohui Liu, Yeshuo Ma, Fei Chen, Wenbin Zeng
Journal: Advanced Healthcare Materials (2025)

Abstract Chronic nonhealing wounds, common in diabetic patients, represent a major clinical challenge, causing significant morbidity and healthcare costs. Persistent bacterial biofilms are a critical obstacle to wound healing, necessitating their effective elimination to promote rapid recovery. In photodynamic antimicrobial therapy (PDAT), enhancing the interaction between the photosensitizer and bacterial biofilms is key to achieving efficient antimicrobial and antibiofilm effects. Here, a novel dissolvable microneedle patch containing a benzoxaborole ( BOB )‐functionalized photosensitizer is designed, TPI‐BOB , for bacteria‐specific targeting and localized PDAT of multidrug‐resistant biofilm infections in diabetic wounds. TPI‐BOB integrates a BOB moiety for selective bacterial binding and a pyridine‐based cationic group to enhance electrostatic interactions, showing superior antimicrobial activity in Gram‐positive bacteria, particularly MRSA . To further optimize therapeutic delivery and combat biofilm‐associated infections, TPI‐BOB is incorporated into dissolvable microneedles, which rapidly disintegrate upon application to wound sites. This microneedle system facilitates localized, efficient delivery of TPI‐BOB to bacterial biofilms, where it triggers photodynamic action under white‐light irradiation. This treatment eradicates the biofilm, initiating tissue repair that reduces inflammation, promotes collagen deposition, and stimulates angiogenesis, accelerating healing. This work presents a novel strategy combining PDAT with microneedle‐mediated drug delivery, offering a promising approach for treating diabetic wounds and other biofilm‐related infections.
Deciphering the transcriptomic landscape of early HR<sup>+</sup>/HER2<sup>−</sup> breast cancer in very young women
Authors: Iris Garrido‐Cano, Marta Tapia, Juan Carbonell, Carlos Peña, Sandra Torres‐Ruiz, Anna Ágreda‐Roca, Ana Lameirinhas, Cristina Tebar, Octavio Burgués, Cristina Hernando, Ana Lluch, Fara Brasó‐Maristany, Aleix Prat, Begoña Bermejo, María Teresa Martínez, Juan Miguel Cejalvo
Journal: Cancer Communications (2025)
Enhancing antitumor immunity through the combination of cholesterolized TLR7 agonist liposomes and radiotherapy: a role for IL‐1β and the inflammasome pathway
Authors: Xuejiao Han, Yuan Cheng, Dandan Wan, Aqu Alu, Ziqi Zhang, Zhenfei Bi, Manni Wang, Yan Tang, Weiqi Hong, Siyuan Chen, Li Chen, Yuquan Wei
Journal: Cancer Communications (2025)

Abstract Background Radiotherapy (RT) is a key treatment modality in cancer therapy, utilizing high‐energy radiation to directly kill tumor cells. Recent research has increasingly highlighted RT's potential to indirectly enhance antitumor immunity. However, this immune activation alone often fails to generate sustained systemic antitumor responses. In this study, we aimed to investigate the antitumor effects of combining cholesterolized toll‐like receptor 7 (TLR7) agonist liposomes, specifically 1V209‐Cho‐Lip, with RT. Methods Mouse tumor models were used to assess the impact of combining 1V209‐Cho‐Lip with RT on tumor progression and modification of the tumor microenvironment. In vitro, primary mouse bone marrow‐derived dendritic cells (BMDCs) were utilized to investigate changes in function and the activated pathways through RNA sequencing. Additionally, we explored the role of oxidized mitochondrial DNA (ox‐mtDNA) released from irradiated tumor cells as a damage‐associated molecular pattern in modulating immune responses. The involvement of interleukin‐1β (IL‐1β) and the inflammasome pathway in the antitumor efficacy of the combined treatment was evaluated using Il‐1β −/− and cysteinyl aspartate specific proteinase 1 knockout ( Casp1 −/− ) mouse models. Results The combination of 1V209‐Cho‐Lip and RT significantly inhibited tumor growth and induced antitumor immunity in tumor models. This combination therapy enhanced maturation, antigen presentation and IL‐1β secretion of dendritic cells (DCs) in vitro. Ox‐mtDNA released from irradiated tumor cells synergized with 1V209‐Cho‐Lip to activate the inflammasome pathway in DCs. The antitumor effect of the combined therapy was significantly reduced in Il‐1β −/− and Casp1 −/− mice. Conclusions This study suggests that the combination of 1V209‐Cho‐Lip with RT might be a promising antitumor strategy and further studies are warranted to explore the clinical relevance of this combination therapy.
A redefined InDel taxonomy provides insights into mutational signatures
Authors: Gene Ching Chiek Koh, Arjun Scott Nanda, Giuseppe Rinaldi, Soraya Boushaki, Andrea Degasperi, Cherif Badja, Andrew Marcel Pregnall, Salome Jingchen Zhao, Lucia Chmelova, Daniella Black, Laura Heskin, João Dias, Jamie Young, Yasin Memari, Scott Shooter, Jan Czarnecki, Matthew Arthur Brown, Helen Ruth Davies, Xueqing Zou, Serena Nik-Zainal
Journal: Nature Genetics (2025)
Single-cell and spatial RNA sequencing identify divergent microenvironments and progression signatures in early- versus late-onset prostate cancer
Authors: Yifei Cheng, Bingxin Liu, Junyi Xin, Xiaobin Wu, Wenchao Li, Jinwei Shang, Jiajin Wu, Zhengdong Zhang, Bin Xu, Mulong Du, Gong Cheng, Meilin Wang
Journal: Nature Aging (2025)
Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy
Authors: Daniel Greene, Koenraad De Wispelaere, Jon Lees, Marta Codina-Solà, Brynjar O Jensson, Emma Hales, Andrea Katrinecz, Esther Nieto Molina, Sonia Pascoal, Rolph Pfundt, Rachel Schot, Marta Sevilla Porras, Frank Sleutels, Irene Valenzuela, Robin Wijngaard, Ignacio Arroyo Carrera, Giles Atton, Didac Casas-Alba, Deirdre Donnelly, Anna Duat Rodríguez, Bárbara Fernández Garoz, Nicola Foulds, Deyanira García-Navas Núñez, Elena González Alguacil, Joanna Jarvis, Sarina G Kant, Irene Madrigal Bajo, Antonio F Martinez-Monseny, Shane McKee, Nelmar Valentina Ortiz Cabrera, Laia Rodríguez-Revenga Bodi, Andrea Sariego Jamardo, Kari Stefansson, Patrick Sulem, Mohnish Suri, Clara Van Karnebeek, Pradeep Vasudevan, Ana Isabel Vega Pajares, Ángel Carracedo, Marc Engelen, Pablo Lapunzina, Natasha P Morgan, Beatriz Morte, Patrick Rump, Kathy Stirrups, Eduardo F Tizzano, Tahsin Stefan Barakat, Michael O'Donoghue, Luis Alberto Pérez-Jurado, Kathleen Freson, Andrew D Mumford, Ernest Turro
Journal: Nature Genetics (2025)
Health effects associated with exposure of children to physical violence, psychological violence and neglect: a Burden of Proof study
Authors: Luisa S Flor, Caroline Stein, Gabriela F Gil, Mariam Khalil, Molly Herbert, Aleksandr Y Aravkin, Alejandra Arrieta, María Jose Baeza de Robba, Flavia Bustreo, Jack Cagney, Renzo J C Calderon-Anyosa, Sinclair Carr, Jaidev Kaur Chandan, Joht Singh Chandan, Carolina V N Coll, Fabiana Martins Dias de Andrade, Gisele N de Andrade, Alexandra N Debure, Erin DeGraw, Ben Hammond, Simon I Hay, Felicia M Knaul, Rachel Q H Lim, Susan A McLaughlin, Nicholas Metheny, Sonica Minhas, Jasleen K Mohr, Erin C Mullany, Christopher J L Murray, Erin M O'Connell, Vedavati Patwardhan, Sofia Reinach, Dalton Scott, Cory N Spencer, Reed J D Sorensen, Heidi Stöckl, Aisha Twalibu, Aiganym Valikhanova, Nádia Vasconcelos, Peng Zheng, Emmanuela Gakidou
Journal: Nature Human Behaviour (2025)
The health effects associated with physical, sexual and psychological gender-based violence against men and women: a Burden of Proof study
Authors: Caroline Stein, Luisa S Flor, Gabriela F Gil, Mariam Khalil, Molly Herbert, Aleksandr Y Aravkin, Alejandra Arrieta, María Jose Baeza de Robba, Flavia Bustreo, Jack Cagney, Renzo J C Calderon-Anyosa, Sinclair Carr, Jaidev Kaur Chandan, Joht Singh Chandan, Carolina V N Coll, Fabiana Martins Dias de Andrade, Gisele N de Andrade, Alexandra N Debure, Erin DeGraw, Ben Hammond, Simon I Hay, Felicia M Knaul, Rachel Q H Lim, Susan A McLaughlin, Nicholas Metheny, Sonica Minhas, Jasleen K Mohr, Erin C Mullany, Christopher J L Murray, Erin M O'Connell, Vedavati Patwardhan, Sofia Reinach, Dalton Scott, Cory N Spencer, Reed J D Sorensen, Heidi Stöckl, Aisha Twalibu, Aiganym Valikhanova, Nádia Vasconcelos, Peng Zheng, Emmanuela Gakidou
Journal: Nature Human Behaviour (2025)
High-Throughput Echocardiography-Guided Induction of Myocardial Ischemia/Reperfusion in Mice
Authors: Florian Sicklinger, Niklas Hartmann, Attila Kovacs, Carla Weinheimer, Jess Nigro, Tobias Thiemann, Junedh Amrute, David Schumacher, Moritz Kornardt, Laura M. Wienecke, Lennart Rompel, Johannes Fischer, John Bachman, Olivia Bedard, Shibali Das, Tim C. Kuhn, Mirko Völkers, Ralf P. Brandes, Rafael Kramann, Nadia Rosenthal, Norbert Frey, Kory J. Lavine, Florian Leuschner
Journal: Circulation Research (2025)

BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice. METHODS: After visualization of the left coronary artery with high-resolution ultrasound imaging and echocardiographic definition of the level of coronary occlusion, the left anterior descending artery was temporarily occluded with 2 micromanipulator-controlled needles. Functional and molecular changes were assessed and compared with commonly performed surgical techniques. RESULTS: Echocardiography-guided induction of myocardial IR enabled standardized induction of myocardial IR injury with subsequent left ventricular remodeling. Incorporation of various quality control measures throughout the procedure ensured a high success rate and the absence of relevant postinterventional mortality in experienced hands. Compared with surgical approaches, echocardiography-guided induction of myocardial IR showed a quicker recovery time and induced a less pronounced inflammatory response characterized by decreased local and systemic neutrophil counts. Notably, infarct size and subsequent post–myocardial infarction cardiac dysfunction were comparable between methods. The novel procedure was successfully implemented at different academic institutions with imaging expertise and demonstrated high interinstitutional reproducibility. CONCLUSIONS: Echocardiography-guided induction of myocardial IR enables high-throughput induction of myocardial IR injury with precise echocardiographic definition of the occlusion level and immediate evaluation of cardiac function during ischemia. The method provides a more clinically relevant assessment of IR sequelae and offers notable animal welfare advantages by eliminating the need for ventilation and thoracotomy, thereby mitigating potential surgery-related confounders.
Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: phase 1/2 and phase 2 trials
Authors: Shen Zhao, Ying Cheng, Qiming Wang, Xingya Li, Jun Liao, Jordi Rodon, Xiangjiao Meng, Yongzhong Luo, Zhendong Chen, Wei Wang, Tienan Yi, Yongsheng Li, Yongmei Yin, Huiting Xu, Guohua Yu, Yanjun Mi, Yun Fan, Zev A Wainberg, Xiang Wang, Cuiyun Su, Qitao Yu, Shuzhen Lai, Longhua Sun, Wu Zhuang, Xian Wang, Jiacheng Yang, Yaling Li, Junyou Ge, Jin Li, Li Zhang, Wenfeng Fang
Journal: Nature Medicine (2025)
Suppression of hypothalamic oestrogenic signal sustains hyperprolactinemia and metabolic adaptation in lactating mice
Authors: Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang
Journal: Nature Metabolism (2025)
Outcomes of Salvage Robotic-assisted Radical Prostatectomy: High-volume Multicentric Data from the European Association of Urology Robotic Urology Section Scientific Working Group
Authors: Marcio Covas Moschovas, Shady Saikali, Marco Sandri, Carlo Bravi, Ugo Falagario, Arjun Nathan, Justin Collins, Eleonora Balestrazzi, Gert de Naeyer, Ruben Groote, Maria Chiara Sighinolfi, Sophie Knipper, Markus Graefen, Randi Pose, Guillaume Ploussard, Hamza Idais, Hubert John, Angelo Mottaran, Riccardo Schiavina, Pietro Piazza, Eugenio Brunocilla, Alberto Breda, Bernardo Rocco, Nina N Harke, Alexandre Mottrie, Senthil Nathan, Vipul Patel, Peter Wiklund
Journal: European Urology (2025)
P-Pev: micelle-like complexes transformed from tumor extracellular vesicles by PEG-PE for personalized therapeutic tumor vaccine
Authors: Hongjian Tian, Wenfeng Zeng, Zihao Wang, Siqi Li, Wenjing Wei, Shanshan Li, Xiaozhe Yin, Wenjing Na, Youwang Wang, Kai Song, Ping Zhu, Wei Liang
Journal: Biomaterials (2025)
Reply to Felix Melchior, Andreas Pircher, and Isabel Heidegger’s Letter to the Editor re: Johann S. de Bono, Meng He, Chen Shi, et al. Final Overall Survival and Molecular Data Associated with Clinical Outcomes in Patients Receiving Ipatasertib and Abiraterone in the Phase 3 IPATential150 Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.12.015
Authors: Christopher Sweeney, Meng He, Matthew Wongchenko, Roberta Ferraldeschi, Johann S de Bono
Journal: European Urology (2025)
The effect of ibrutinib on the myeloid cell compartment in CNS lymphoma
Authors: Julia C Kuehn, Nicolas N Neidert, Junyi Zhang, Jurik Mutter, Stefan Alig, Christian Klingler, Fabian Hummel, Lavanya Ranganathan, Sabine Bleul, Jürgen Beck, Marco Prinz, Maximilian Diehn, Ash Alizadeh, Justus Duyster, Roman Sankowski, Dieter H Heiland, Florian Scherer
Journal: Leukemia (2025)
Neural crest-associated gene FOXD1 induces an immunosuppressive microenvironment by regulating myeloid-derived suppressor cells in melanoma
Authors: Qian Sun, Nina Wang, Juliane Poelchen, Mareike Peter, Daniel Novak, Feyza Gül Özbay Kurt, Rebekka Bitsch, Huizi Wu, Yiman Wang, Sandra Pardo, Rui Han, Shibo Liu, Lidong Gong, Yuxin Zhang, Kilian Wistuba-Hamprecht, Viktor Umansky, Jochen Sven Utikal
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Neural crest-associated genes play pivotal roles in tumor initiation, progression, and the intricate dynamics of the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSC) within the TME are important in dampening T cell activity and contributing to resistance against immunotherapeutic interventions. The neural crest-associated gene Forkhead Box D1 (FOXD1) has been identified as an oncogenic factor that induces melanoma dedifferentiation and progression. However, the underlying mechanisms and the impact of FOXD1 on the antitumor immune response remain unclear. Methods To investigate the impacts of FOXD1 on the melanoma microenvironment, we analyzed publicly available datasets from multiple platforms, including TNMplot, TIMER2.0, etc. In addition, FOXD1 was overexpressed (OE) or knocked down in melanoma cells to identify its biological functions in vitro and in vivo. Flow cytometry and arginase activity assay were used to analyze the phenotype and function of MDSC. Western blot, reverse transcription-PCR, or ELISA assays were employed to analyze the expression of FOXD1 and its downstream effectors. In vivo experiments were conducted to investigate the role of FOXD1 in melanoma progression and the influence on MDSC accumulation within the TME. Results We demonstrate that increased FOXD1 levels inversely correlated with melanoma responsiveness to immunotherapy. Ex-vivo analyses unveiled that monocytes, exposed to conditioned medium from FOXD1-OE melanoma cells, effectively suppressed T cell proliferation and upregulated the expression of programmed death-ligand 1 (PD-L1) and other immunosuppressive factors. FOXD1 was identified as a direct regulator of interleukin 6 (IL6) expression, which is pivotal for MDSC induction. Blocking IL6 reversed MDSC-associated immunosuppression. Additionally, miR-581, a potential negative regulator of FOXD1, attenuated the impact of FOXD1 on IL6 expression and MDSC differentiation. In vivo experiments demonstrated that tumors derived from FOXD1 OE melanoma cells contained a significantly higher frequency of PD-L1 + MDSC compared with controls, while FOXD1 knockdown resulted in reduced tumor growth and diminished MDSC accumulation. Conclusion Our study elucidated a novel function of FOXD1 in melanoma pathogenesis, highlighting its role in orchestrating the immunosuppressive TME by promoting the generation of MDSC via IL6 upregulation.
Tumor-infiltrating lymphocyte immunotherapy comes of age: a journey of development in the Surgery Branch, NCI
Authors: Stephanie L Goff, Steven A Rosenberg
Journal: Journal for ImmunoTherapy of Cancer (2025)

The early development of tumor-infiltrating lymphocytes into an effective clinical strategy was fundamentally the work of hundreds of scientists and clinicians within the Surgery Branch of the National Cancer Institute under the leadership of Steven Rosenberg. That journey brought new insights into the tumor–immune cell interface and ultimately helped create a new first-in-class therapeutic for patients with metastatic cancer.
Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review
Authors: Gils Roex, Khloe S Gordon, Eva Lion, Michael E Birnbaum, Sébastien Anguille
Journal: Journal for ImmunoTherapy of Cancer (2025)

Chimeric antigen receptor (CAR)-T-cell therapy has been highly successful in the treatment of B-cell hematological malignancies. CARs are modular synthetic molecules that can redirect immune cells towards target cells with antibody-like specificity. Despite their modularity, CARs used in the clinic are currently composed of a limited set of domains, mostly derived from IgG, CD8α, 4-1BB, CD28 and CD3ζ. The current low throughput CAR screening workflows are labor-intensive and time-consuming, and lie at the basis of the limited toolbox of CAR building blocks available. High throughput screening methods facilitate simultaneous investigation of hundreds of thousands of CAR domain combinations, allowing discovery of novel domains and increasing our understanding of how they behave in the context of a CAR. Here we review the growing body of reports that employ these high throughput screening and computational methods to advance CAR design. We summarize and highlight the important differences between the different studies and discuss their limitations and future considerations for further improvements. In conclusion, while still in its infancy, high throughput screening of CARs has the capacity to vastly expand the CAR domain toolbox and improve our understanding of CAR design. This knowledge could be foundational for translating CAR therapy beyond hematological malignancies and push the frontiers in personalized medicine.
Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin’s lymphoma
Authors: Charlotte Junkuhn, Phillip Schiele, Anna Luzie Walter, Frederik Hamm, Benedikt Obermayer, David Busch, Andrea Stroux, Mareike Frick, Olaf Penack, Frederik Damm, Julia Polansky, Lars Bullinger, Annette Künkele, Marco Frentsch, Il-Kang Na
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Chimeric antigen receptor (CAR) T-cell therapy depends on T cells that are genetically modified to recognize and attack cancer cells. Their effectiveness thus hinges on the functionality of a patient’s own T cells. Since CAR T-cell therapy is currently only approved for advanced cancers after at least one line of chemotherapy, we evaluated the potential negative effects of prior exposure to chemotherapy on T-cell functionality. Methods We studied T cells of two B-cell non-Hodgkin’s lymphoma patient cohorts, one collected before treatment (pre-therapy) and the other after one or more (median 3) lines of chemotherapy (post-therapy). Leveraging advanced multiparameter flow cytometry, single-cell RNA sequencing (scRNA-seq), whole-genome DNA methylation arrays and in vitro functionality testing of generated CAR T cells, we compared patient samples in their suitability for effective CAR T-cell therapy. Results We discovered significant modifications in T-cell subsets and their transcriptional profiles secondary to chemotherapy exposure. Our analysis revealed a discernible shift towards phenotypically more differentiated T cells and an upregulation of markers indicative of T-cell exhaustion. Additionally, scRNA-seq and DNA methylation analyses revealed gene expression and epigenetic changes associated with diminished functionality in post-therapy T cells. Cytotoxicity assays demonstrated superior killing efficacy of CAR T cells derived from treatment-naïve patients compared with those with chemotherapy history. Conclusions These findings corroborate that employing T cells collected prior to frontline chemotherapy could enhance the effectiveness of CAR T-cell therapy and improve patient outcomes.
Application of biodegradable implants in pediatric orthopedics: shifting from absorbable polymers to biodegradable metals
Authors: Yunan Lu, Ting Zhang, Kai Chen, Federico Canavese, Chenyang Huang, Hongtao Yang, Jiahui Shi, Wubing He, Yufeng Zheng, Shunyou Chen
Journal: Bioactive Materials (2025)