tbuckley/cabot-search huggingface dataset:
Dissecting the immune landscape in pediatric high-grade glioma reveals cell state changes under therapeutic pressure
Authors: Jenna J LaBelle, Rebecca D Haase, Alexander Beck, Jacob Haase, Li Jiang, Carlos Alberto Oliveira de Biagi, Sina Neyazi, Bernhard Englinger, Ilon Liu, Maria Trissal, Daeun Jeong, Olivia A Hack, Andrezza Nascimento, McKenzie L Shaw, Cuong M Nguyen, Sophia Castellani, Nathan D Mathewson, Orr Ashenberg, Gustavo Alencastro Veiga Cruzeiro, Tom Rosenberg, Jayne R Vogelzang, Jason Pyrdol, Sascha Marx, Adrienne M Luomo, Anze Godicelj, Alicia Baumgartner, Jacob S Rozowsky, Sibylle Madlener, Lisa Mayr, Andreas Peyrl, Rene Geyeregger, Daniela Loetsch, Christian Dorfer, Christine Haberler, Natalia Stepien, Irene Slavc, Tom Belle Davidson, Robert M Prins, Kee Kiat Yeo, Tabitha Cooney, Keith Ligon, Hart Lidov, Sanda Alexandrescu, Lissa C Baird, Johannes Gojo, Kai W Wucherpfennig, Mariella G Filbin
Journal: Cell Reports Medicine (2025)

Pediatric high-grade gliomas (pHGGs) are among the most lethal childhood tumors. While therapeutic approaches were largely adapted from adult treatment regime, significant biological differences between pediatric and adult gliomas exist, which influence the immune microenvironment and may contribute to the limited response to current pHGG treatment strategies. We provide a comprehensive transcriptomic analysis of the pHGG immune landscape using single-cell RNA sequencing and spatial transcriptomics. We analyze matched malignant, myeloid, and T cells from patients with pediatric diffuse high-grade glioma (HGG) or high-grade ependymoma, examining immune microenvironment distinctions after chemo-/radiotherapy, immune checkpoint inhibition treatment, and by age. Our analysis reveals differences in the proportions of pediatric myeloid subpopulations compared to adult counterparts. Additionally, we observe significant shifts toward immune-suppressive environments following cancer therapy. Our findings offer valuable insights into potential immunotherapy targets and serve as a robust resource for understanding immune microenvironmental variations across HGG age groups and treatment regimens.
An engineered gut bacterium protects against dietary methylmercury exposure in pregnant mice
Authors: Kristie B Yu, Franciscus Chandra, Elena J Coley-O'Rourke, Erik T Paulson, Anna Novoselov, David Zhang, Delanie Finnigan, Jorge Paramo, Arlene Lopez-Romero, Tien S Dong, Amina T Schartup, Elaine Y Hsiao
Journal: Cell Host & Microbe (2025)
Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma
Authors: Xiu-Feng Liu, Bin Song, Chang-Bin Sun, Qian Zhu, Jian-Hui Yue, Yu-Jing Liang, Jia He, Xi-Liang Zeng, Ye-Chi Qin, Qiu-Yan Chen, Hai-Qiang Mai, Xi Zhang, Jiang Li
Journal: Cell Reports Medicine (2025)

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3+ T cell clusters within 26 TIL infusion products: 11 CD3+CD8+ TILs, 2 CD3+CD4+ TILs, and 1 CD3+CD8-CD4- double-negative (DN) TIL. (DN) TILs, significantly associated with poor TIL-ACT outcomes, exhibit an activated regulatory T cell-like phenotype and include two CD56+ and four CD56- subsets. Among them, CD56-KZF2+ (DN) TILs are predominantly suppressive. (DN) TILs inhibit CD8+ TIL expansion via Fas-FasL, transforming growth factor β (TGF-β), and interleukin (IL)-10 signaling. Distinct CD8+ T subsets differentially impact on TIL-ACT outcomes, while 9 baseline TME gene signatures and 14 intracellular T cell genes hold prognostic value. Our findings identify predictive TIL subsets and biomarkers for TIL-ACT outcomes.
Enhanced sequential osteosarcoma therapy using a 3D-Printed bioceramic scaffold combined with 2D nanosheets via NIR-II photothermal-chemodynamic synergy
Authors: Guangyu Jian, Si Wang, Xinlu Wang, Qinyi Lu, Xingyu Zhu, Shucheng Wan, Shan Wang, Dize Li, Chao Wang, Qingqing He, Tao Chen, Jinlin Song
Journal: Bioactive Materials (2025)
Defining the role of pragmatic clinical trials in cancer clinical research: outcomes of a collaborative workshop hosted by the European Organisation for Research and Treatment of Cancer
Authors: Fábio Cardoso Borges, Winette T A van der Graaf, Robbe Saesen, Stefan Aebi, Ana E Amariutei, Justin Bekelman, Thierry Gorlia, Frank Hulstaert, Isabelle Huys, Paul Kluetz, Michael J Morris, Vijay Patil, Sheila A Prindiville, Richard L Schilsky, Andrew Thomson, Shaun Treweek, Michael Weller, Mira Zuidgeest, Valesca Retel, Denis Lacombe
Journal: The Lancet Oncology (2025)
Cancer therapy‐related cardiotoxicity is associated with distinct alterations of the myocardial lipidome
Authors: Vera M. Braun, Anna Foryst‐Ludwig, Ulf Landmesser, István Baczkó, Hendrik Milting, Ulrich Kintscher, Niklas Beyhoff
Journal: European Journal of Heart Failure (2025)

Anthracyclines are key components of various chemotherapy regimens, but their clinical utility is limited by severe cardiotoxic side effects. Previous studies have suggested that anthracycline-induced cardiotoxicity (AIC) may be driven by alterations in myocardial lipid metabolism. This study aimed to systematically explore the cardiac lipidomic landscape of AIC with regard to potential pathomechanisms and novel therapeutic targets. Mass spectrometry-based untargeted lipidomics were performed on myocardial biopsies from 13 patients with AIC (age 53 ± 31 years, 54% female, left ventricular ejection fraction 19 ± 4%) and 15 age- and sex-matched controls. Lipidomic profiles were also compared with 15 patients with other heart failure aetiologies (matched for sex and age). A total of 627 individual lipid species from 22 different lipid classes were analysed. AIC was associated with a lower proportion of polyunsaturated fatty acids towards more monounsaturated and saturated sidechains as well as significant alterations in the proportion of odd-chain fatty acids. Pathway analyses indicated a higher precursor conversion into lysolipids in AIC. This accumulation of lysolipid species was not observed in other heart failure aetiologies and may represent a specific finding in AIC. Anthracycline-induced cardiotoxicity leads to distinct alterations of the myocardial lipidome. Increased levels of myocardial lysolipids were identified as a novel lipidomic trait in AIC, which appears to be distinct from other causes of heart failure. Further research studying pharmacological interventions in lysolipid metabolism for prevention and therapy of AIC is warranted.
Multilayer cascade-response nanoplatforms as metabolic symbiotic disruptors to reprogram the immunosuppressive microenvironment
Authors: Rui Liu, Lu Guo, Dandan Shi, Xiao Sun, Mengmeng Shang, Yading Zhao, Xiaoxuan Wang, Yuanyuan Yang, Shan Xiao, Jie Li
Journal: Journal of Controlled Release (2025)
<i>Notes from the Field:</i> Suspected Medetomidine Withdrawal Syndrome Among Fentanyl-Exposed Patients — Philadelphia, Pennsylvania, September 2024–January 2025
Authors: Samantha Huo, Kory London, Lauren Murphy, Emily Casey, Philip Durney, Maya Arora, Rita McKeever, Abriana Tasillo, Dennis Goodstein, Brendan Hart, Jeanmarie Perrone
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Overdoses Involving Medetomidine Mixed with Opioids — Chicago, Illinois, May 2024
Authors: Amy Nham, John N. Le, Shawn A. Thomas, Kimberly Gressick, Emily N. Ussery, Jean Y. Ko, R. Matt Gladden, Christina A. Mikosz, Joshua G. Schier, Alana Vivolo-Kantor, Maria Fiorillo, McKenna McMaster, Darlene Nolasco Magana, Livia Verklan-McInnes, Michael Wahl, Taylor Wood, Axel Adams, Alex Krotulski, Jordan Trecki, Ross Ellison, Roy Gerona, Ponni Arunkumar, Mojde Mir, Leslie M. Wise, Emma Betancourt, Kathleen Monty, Jhoanna Gulmatico, Angie Pojas, Ruchi Fitzgerald, Miao Hua
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Medetomidine, a nonopioid sedative not approved for use in humans, has periodically been detected in illegally manufactured opioids across North America since 2022. On May 11, 2024, the Chicago Department of Public Health (CDPH) and the Illinois Department of Public Health were alerted by hospitals and the Illinois Poison Center to an increase in emergency medical services responses for suspected opioid-involved overdoses with atypical symptoms, mostly clustered on Chicago's West Side. CDPH and CDC investigated and identified 12 confirmed, 26 probable, and 140 suspected overdoses involving medetomidine mixed with opioids among patients treated at three hospitals in Chicago's West Side during May 11-17, 2024. Medetomidine had not been previously identified in Chicago's illegal drug supply. Fentanyl was identified in all drug samples and blood specimens containing medetomidine. Most patients were male, non-Hispanic Black or African American, and aged 45-64 years; most patients with confirmed cases experienced bradycardia and had no or only a partial response to naloxone. This cluster is the largest reported for confirmed medetomidine-involved overdoses. Multisector surveillance, including by health care providers, toxicology laboratories, and public health personnel, was essential for quickly identifying and responding to new adulterants in the illegal drug supply. Because all specimens and samples in this investigation that contained medetomidine also contained natural or synthetic opioids, administering naloxone for all suspected opioid-involved overdoses remains crucial.
<i>Notes from the Field:</i> Severe Medetomidine Withdrawal Syndrome in Patients Using Illegally Manufactured Opioids — Pittsburgh, Pennsylvania, October 2024–March 2025
Authors: Simon J. Ostrowski, Kenichi Tamama, William J. Trautman, Darien L. Stratton, Michael J. Lynch
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Targeting the MAP kinase pathway in colorectal cancer: A journey in personalized medicine
Authors: Jordan W. Appleyard, Christopher J.M. Williams, Paolo Manca, Filippo Pietrantonio, Jenny F. Seligmann
Journal: Clinical Cancer Research (2025)

The anti-EGFR agents, cetuximab and panitumumab, were the first targeted agents to be licensed in colorectal cancer and marked a significant advancement in personalized care. Initial biomarkers provided poor discrimination between responders and non-responders. Through hypothesis-led translational studies, tumor genomic negative predictive markers were identified, and treatment is now limited to patients with RAS and BRAF wild-type disease. Guidelines further recommend treatment limitation to those with left-primary tumor location (PTL). Despite such progress, anti-EGFR response remains variable within the biomarker-selected population, indicating the presence of additional mechanisms of resistance and underscoring the need for novel positive predictive biomarkers, and novel targeted agents. This review explores established and emerging predictive biomarkers of anti-EGFR efficacy, including tumor genetic alterations beyond RAS and BRAF, as well as the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG). To date, biomarker discovery and validation have largely been performed within post hoc analyses of existing clinical trial datasets. We highlight ongoing prospective clinical trials aiming to validate earlier findings and describe how novel biomarkers are being used to re-evaluate anti-EGFR agents in treatment settings where earlier trials, among non-biomarker selected populations, yielded negative results - including right-PTL, locally advanced disease, and anti-EGFR rechallenge strategies. Additionally, we discuss how our improved understanding of the molecular mechanisms underpinning anti-EGFR response and resistance is being leveraged to develop novel targeted agents.
Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma
Authors: Michael Wang, David Salek, David Belada, Yuqin Song, Wojciech Jurczak, Brad S. Kahl, Jonas Paludo, Michael P. Chu, Iryna Kryachok, Laura Fogliatto, Chan Y. Cheah, Marta Morawska, Juan-Manuel Sancho, Yufu Li, Caterina Patti, Cecily Forsyth, Jingyang Zhang, Robin Lesley, Safaa Ramadan, Simon Rule, Martin Dreyling
Journal: Journal of Clinical Oncology (2025)

BACKGROUND: The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival, but without improvement to overall survival likely due to toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL.METHODS: Patients aged ≥65 years with previously untreated mantle cell lymphoma received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus 6 cycles of bendamustine (90 mg/m2; days 1 and 2) and rituximab (375 mg/m2; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. Primary endpoint was progression-free survival per independent review committee; overall response rate and overall survival were secondary endpoints.RESULTS: In total, 598 patients were randomized, with 299 in each arm. At a median follow-up of 44.9 months, median progression-free survival was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio, 0.73; 95% confidence interval, 0.57 to 0.94; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. Overall survival was not significantly different (hazard ratio, 0.86; 95% confidence interval, 0.65 to 1.13; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively.CONCLUSIONS: Combination of acalabrutinib with bendamustine-rituximab significantly improved progression-free survival. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.
Improved Transplant Outcomes With Alternative Donors in Myelofibrosis: A 20‐Year Japanese Registry Analysis of Donor Sources and the Impact of Ruxolitinib
Authors: Kazuki Sakatoku, Hirohisa Nakamae, Makoto Murata, Yutaka Shimazu, Katsuto Takenaka, Fumihiko Kimura, Naoyuki Uchida, Tetsuya Nishida, Takahiro Fukuda, Noriko Doki, Jun Ishikawa, Emiko Sakaida, Keisuke Kataoka, Shuichi Shirane, Masatsugu Tanaka, Hikaru Kobayashi, Masashi Sawa, Toshio Wakayama, Noboru Asada, Yasufumi Uehara, Makoto Yoshimitsu, Junya Kanda, Marie Ohbiki, Yoshiko Atsuta, Takayoshi Tachibana
Journal: American Journal of Hematology (2025)

This study of 308 myelofibrosis patients shows that in recent years (2013-2019), alternative donors (mismatched unrelated donors and cord blood) achieved survival rates comparable to HLA-matched donors-a significant improvement compared to earlier years (2000-2012) when outcomes differed substantially. Ruxolitinib showed significant benefits in older patients (≥ 57), particularly with mismatched unrelated donors. Cord blood transplantation outcomes improved with MMF-based GVHD prophylaxis. These findings suggest optimized strategies combining both age-specific and donor-specific approaches can maximize transplant success in myelofibrosis patients.
Tebentafusp elicits on-target cutaneous immune responses driven by cytotoxic T-cells in uveal melanoma patients
Authors: Ramon Staeger, Aizhan Tastanova, Adhideb Ghosh, Nicola Winkelbeiner, Prachi Shukla, Isabel Kolm, Patrick Turko, Adel Benlahrech, Jane Harper, Anna Broomfield, Antonio Camera, Marianna Ambrosio, Veronika Haunerdinger, Phil F Cheng, Egle Ramelyte, James P Pham, Stefanie Kreutmair, Burkhard Becher, Mitchell P Levesque, Reinhard Dummer, Barbara Meier-Schiesser
Journal: Journal of Clinical Investigation (2025)

Tebentafusp is the first T-cell receptor-based bispecific protein approved for clinical use in HLA-A*02:01+ adult patients with unresectable/metastatic uveal melanoma. It redirects T-cells toward gp100-expressing target cells, frequently inducing skin-related early adverse events. This study investigated immunological and cellular responses using single-cell and spatial analysis of skin biopsies from patients with metastatic uveal melanoma treated with tebentafusp. 81.8% of patients developed acute cutaneous adverse events, which correlated with improved survival. Multimodal analysis revealed a brisk infiltration of CD4+ and CD8+ T-cells, while melanocyte numbers declined. Single-cell RNA-sequencing revealed T-cell activation, proliferation, and IFN-γ/cytotoxic gene upregulation. CD8+ T-cells co-localized with melanocytes and upregulated LAG3, suggesting potential for combination therapies with tebentafusp. Melanocytes upregulated antigen presentation and apoptotic pathways, while pigmentation gene expression decreased. However, gp100 remained stably expressed. Sequential skin biopsies enable in vivo pharmacodynamic modeling of tebentafusp, offering insights into immune activation, toxicity, and treatment response. Examining the on-target effects of bispecifics in tissues amenable to longitudinal sampling enhances our understanding of toxicity and therapeutic escape mechanisms, guiding strategies for treatment optimization.
Autonomously Functioning Thyroid Nodule With 99mTc-PSMA Uptake in a Patient With Prostate Cancer
Authors: Mohammad Hadi Samadi, Pegah Sahafi, Mohammad Ahmadi, Susan Khezri, Somaye Barashki
Journal: Clinical Nuclear Medicine (2025)

We present the findings of a 99mTc-PSMA scan in a 76-year-old man with a history of prostate cancer. He was referred for re-staging and response to treatment. The 99mTc-HYNIC PSMA scan incidentally detected an area of increased uptake in the neck region. Subsequent SPECT/CT imaging revealed a large, heterogeneous PSMA-avid thyroid nodule with macrocalcification, suggesting a benign thyroid nodule. Comprehensive imaging confirmed hyperthyroidism with a large autonomously functioning nodule. The case underscores the importance of recognizing PSMA uptake in benign thyroid lesions, emphasizing the need for a thorough evaluation to prevent misdiagnosis and ensure appropriate management.
The multiverse of CD46 and oncologic interactions
Authors: M. Kathryn Liszewski, John P. Atkinson
Journal: Journal of Clinical Investigation (2025)

Initially identified as a regulator of complement activation on host cells, the known roles of CD46 (membrane cofactor protein [MCP]) have expanded. We now know that this ancient molecule is expressed on almost all nucleated cells as a family of four predominant isoforms. It also is involved in human reproduction, modulation of T cell activation and immunoinflammatory effector functions, autophagy, and the newly identified intracellular complement system (complosome). CD46 is also known as a "pathogen" magnet, being a port of entry for at least seven bacteria and five viruses. Moreover, CD46 has recently emerged as a key player in cancer biology. Numerous studies provide evidence of the association among elevated CD46 expression, malignant transformation, and metastasizing potential. These features, along with its roles as pathogen receptor, have made CD46 a target for cancer therapeutics. Thus, modified viral vectors (such as strains of adenovirus and measles virus) targeting CD46 currently are being exploited against a wide range of cancers. Another oncologic treatment utilizes a CD46-targeting human mAb as an antibody-drug conjugate. Herein, we review CD46 and its "multiverse" of cancer interactions.
Collagen type VI regulates TGF-β bioavailability in skeletal muscle in mice
Authors: Payam Mohassel, Hailey Hearn, Jachinta Rooney, Yaqun Zou, Kory Johnson, Gina Norato, Matthew A Nalls, Pomi Yun, Tracy Ogata, Sarah Silverstein, David A Sleboda, Thomas J Roberts, Daniel B Rifkin, Carsten G Bönnemann
Journal: Journal of Clinical Investigation (2025)

Collagen VI-related disorders (COL6-RDs) are a group of rare muscular dystrophies caused by pathogenic variants in collagen VI genes (COL6A1, COL6A2, and COL6A3). Collagen type VI is a heterotrimeric, microfibrillar component of the muscle extracellular matrix (ECM), predominantly secreted by resident fibroadipogenic precursor cells in skeletal muscle. The absence or mislocalization of collagen VI in the ECM underlies the noncell-autonomous dysfunction and dystrophic changes in skeletal muscle with a yet elusive direct mechanistic link between the ECM and myofiber dysfunction. Here, we conducted a comprehensive natural history and outcome study in a mouse model of COL6-RDs (Col6a2-/- mice) using standardized (TREAT-NMD) functional, histological, and physiological parameters. Notably, we identify a conspicuous dysregulation of the TGF-β pathway early in the disease process and propose that the collagen VI-deficient matrix is not capable of regulating the dynamic TGF-β bioavailability both at baseline and in response to muscle injury. Thus, we propose a new mechanism for pathogenesis of the disease that links the ECM regulation of TGF-β with downstream skeletal muscle abnormalities, paving the way for the development and validation of therapeutics that target this pathway.
Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease
Authors: Jacob A. Torres, Mina Rezaei, Caroline Broderick, Louis Lin, Xiaofang Wang, Bernd Hoppe, Benjamin D. Cowley, Vincenzo Savica, Vicente E. Torres, Saeed Khan, Ross P. Holmes, Michal Mrug, Thomas Weimbs
Journal: Journal of Clinical Investigation (2025)
Exceptional Response to Rechallenge Peptide Receptor Radionuclide Therapy in Metastatic Carotid Body Tumor
Authors: Piyush Aggarwal, Swayamjeet Satapathy, Bidya Sarungbam, Ashwani Sood, Rajender Kumar, Shikha Goyal, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2025)

Carotid body tumor (CBT) is the most common head and neck paraganglioma with the very rare occurrence of distant metastases. The widespread distant metastases in head and neck paraganglioma have limited treatment options, with peptide receptor radionuclide therapy (PRRT) being an effective treatment in somatostatin receptor-expressing lesions. Here is a case of a 45-year-old woman with metastatic CBT who showed excellent response initially to 177Lu-DOTATATE PRRT, but presented later in wheel-chair bound condition with metastatic lesions and spinal cord compression at multiple levels, which again showed exceptional response to rechallenge PRRT.