tbuckley/cabot-search huggingface dataset:
Endosialin-positive CAFs promote hepatocellular carcinoma progression by suppressing CD8<sup>+</sup>T cell infiltration
Authors: Lunbiao Gan, Tong Lu, Yu Lu, Hongtao Song, Jiayu Zhang, Keying Zhang, Shiqi Lu, Xinjie Wu, Fengze Nie, Sijia Di, Donghui Han, Fa Yang, Weijun Qin, Weihong Wen
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background and aims Endosialin, also known as tumor endothelial marker1 or CD248, is a transmembrane glycoprotein that is mainly expressed in cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC). Our previous study has found that endosialin-positive CAFs could recruit and induce the M2 polarization of macrophages in HCC. However, whether they may regulate other types of immune cells to promoting HCC progression is not known. Approach and results The growth of both subcutaneous and orthotopic HCC tumors was significantly inhibited in endosialin knockout (EN KO ) mice. Single-cell sequencing and flow cytometry analysis showed that tumor tissues from EN KO mice had increased CD8 + T cell infiltration. Mixed HCC tumor with Hepa1-6 cells and endosialin knockdown fibroblasts also showed inhibited growth and increased CD8 + T cell infiltration. Data from in vitro co-culture assay, chemokine array and antibody blocking assay, RNA-seq and validation experiments showed that endosialin inhibits the phosphorylation and nuclear translocation of STAT1 in CAFs. This inhibition leads to a decrease in CXCL9/10 expression and secretion, resulting in the suppression of CD8 + T cell infiltration. High level of endosialin protein expression was correlated with low CD8 + T infiltration in the tumor tissue of HCC patients. The combination therapy of endosialin antibody and PD-1 antibody showed synergistic antitumor effect compared with either antibody used individually. Conclusions Endosialin could inhibit CD8 + T cell infiltration by inhibiting the expression and secretion of CXCL9/10 in CAFs, thus promote HCC progression. Combination therapy with endosialin antibody could increase the antitumor effect of PD-1 antibody in HCC, which may overcome the resistance to PD-1 blockade.
Rocuronium-specific antibodies drive perioperative anaphylaxis but can also function as reversal agents in preclinical models
Authors: Alice Dejoux, Qianqian Zhu, Christelle Ganneau, Odile Richard-Le Goff, Ophélie Godon, Julien Lemaitre, Francis Relouzat, François Huetz, Aurélien Sokal, Alexis Vandenberghe, Cyprien Pecalvel, Lise Hunault, Thomas Derenne, Caitlin M. Gillis, Bruno Iannascoli, Yidan Wang, Thierry Rose, Christel Mertens, Pascale Nicaise-Roland, Patrick England, Matthieu Mahévas, Luc de Chaisemartin, Roger Le Grand, Hélène Letscher, Frederick Saul, Cédric Pissis, Ahmed Haouz, Laurent L. Reber, Pascal Chappert, Friederike Jönsson, Didier G. Ebo, Gaël A. Millot, Sylvie Bay, Sylvie Chollet-Martin, Aurélie Gouel-Chéron, Pierre Bruhns, David A. Mancardi, Vanessa Granger, Dan Longrois, Philippe Montravers, Caroline Sauvan, Michel Aubier, Catherine Neukirch, Fadia Dib, Catherine Paugam-Burtz, Skander Necib, Hawa Keita-Meyer, Valentina Faitot, Alexandre Mebazaa, Matthieu Le Dorze, Bernard Cholley, Jean Mantz, Olivier Langeron, Sabrine Roche, Laurent Jacob, Benoit Plaud, Julie Bresson, Carole Chahine, Marc Fischler, Marie-Thérèse Guinnepain, Florence Tubach, Antoine Mignon
Journal: Science Translational Medicine (2024)

Neuromuscular blocking agents (NMBAs) relax skeletal muscles to facilitate surgeries and ease intubation but can lead to adverse reactions, including complications because of postoperative residual neuromuscular blockade (rNMB) and, in rare cases, anaphylaxis. Both adverse reactions vary between types of NMBAs, with rocuronium, a widely used nondepolarizing NMBA, inducing one of the longest rNMB durations and highest anaphylaxis incidences. rNMB induced by rocuronium can be reversed by the synthetic γ-cyclodextrin sugammadex. However, in rare cases, sugammadex can provoke anaphylaxis. Thus, additional therapeutic options are needed. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies. To understand the pathogenesis of rocuronium-induced anaphylaxis and to identify potential therapeutics, we investigated the memory B cell antibody repertoire of patients with suspected hypersensitivity to rocuronium. We identified polyclonal antibody repertoires with a high diversity among V(D)J genes without evidence of clonal groups. When recombinantly expressed, these antibodies demonstrated specificity and low affinity for rocuronium without cross-reactivity for other NMBAs. Moreover, when these antibodies were expressed as human immunoglobulin E (IgE), they triggered human mast cell activation and passive systemic anaphylaxis in transgenic mice, although their affinities were insufficient to serve as reversal agents. Rocuronium-specific, high-affinity antibodies were thus isolated from rocuronium-immunized mice. The highest-affinity antibody was able to reverse rocuronium-induced neuromuscular blockade in nonhuman primates with kinetics comparable to that of sugammadex. Together, these data support the hypothesis that antibodies cause anaphylactic reactions to rocuronium and pave the way for improved diagnostics and neuromuscular blockade reversal agents.
HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis
Authors: Ishtiaq Jeelani, Jae-Su Moon, Flavia Franco da Cunha, Chanond A. Nasamran, Seokhyun Jeon, Xinhang Zhang, Gautam K. Bandyopadhyay, Katarzyna Dobaczewska, Zbigniew Mikulski, Mojgan Hosseini, Xiao Liu, Tatiana Kisseleva, David A. Brenner, Seema Singh, Rohit Loomba, Minkyu Kim, Yun Sok Lee
Journal: Science Translational Medicine (2024)

Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow–derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation. However, the molecular mechanisms underlying these changes in KCs are not known. Here, we show that hypoxia-inducible factor 2α (HIF-2α) mediates NASH-associated decreased KC growth and efferocytosis by enhancing lysosomal stress. At the molecular level, HIF-2α stimulated mammalian target of rapamycin (mTOR)– and extracellular signal–regulated kinase-dependent inhibitory transcription factor EB (TFEB) phosphorylation, leading to decreased lysosomal and phagocytic gene expression. With increased metabolic stress and phago/efferocytic burden in NASH, these changes were sufficient to increase lysosomal stress, causing decreased efferocytosis and lysosomal cell death. Of interest, HIF-2α–dependent TFEB regulation only occurred in KCs but not RHMs. Instead, in RHMs, HIF-2α promoted mitochondrial reactive oxygen species production and proinflammatory activation by increasing ANT2 expression and mitochondrial permeability transition. Consequently, myeloid lineage–specific or KC-specific HIF-2α depletion or the inhibition of mTOR-dependent TFEB inhibition using antisense oligonucleotide treatment protected against the development of NASH in mice. Moreover, treatment with an HIF-2α–specific inhibitor reduced inflammatory and fibrogenic gene expression in human liver spheroids cultured under a NASH-like condition. Together, our results suggest that macrophage subtype–specific effects of HIF-2α collectively contribute to the proinflammatory activation of liver macrophages, leading to the development of NASH.
Second primary malignancies after CAR T-cell therapy: A systematic review and meta-analysis of 5,517 lymphoma and myeloma patients
Authors: Tobias Tix, Mohammad Alhomoud, Roni Shouval, Edward R. Scheffer Cliff, Miguel-Angel Perales, David M. Cordas dos Santos, Kai Rejeski
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Chimeric antigen receptor (CAR) T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events, including second primary malignancies (SPM) that impact morbidity and mortality. To delineate the frequency and subtypes of SPMs following CAR-T in lymphoma and myeloma, we performed a systematic review and meta-analysis. Experimental Design: A literature search was conducted in the MEDLINE, Embase, and Cochrane CENTRAL databases. Following the extraction of SPM cases and assignment of malignant origin, we analyzed SPM point estimates using random effects models. Results: We identified 326 SPMs across 5,517 patients from 18 clinical trials and 7 real-world studies. With a median follow-up of 21.7 months, the overall SPM point estimate was 6.0% (95% confidence interval, 4.8%–7.4%). SPM estimates were associated with treatment setting (clinical trials &amp;gt; real-world studies), duration of follow-up, and number of prior treatment lines, which were each confirmed as independent study-level risk factors of SPM in a meta-regression model. A subgroup meta-analysis of the four trials that randomized CAR-T versus standard-of-care revealed a similar risk of SPM with either treatment strategy (P = 0.92). In a distribution analysis of SPM subtypes, hematologic malignancies were the most common entity (37%), followed by solid tumors (27%) and non-melanoma skin cancers (16%). T-cell malignancies represented a small minority of events (1.5%). We noted disease- and product-specific variations in SPM distribution. Conclusions: These data raise awareness of SPM as a clinically relevant long-term adverse event in patients receiving CAR T-cell therapy. However, our findings do not indicate that SPM frequency is higher with CAR-T versus previous standard-of-care strategies.
CXCR4-Targeted PET Imaging in Hematologic Malignancies
Authors: Mohammadreza Chavoshi, Seyed Ali Mirshahvalad, Andres Kohan, Claudia Ortega, Ur Metser, Adam Farag, Robert Kridel, David Hodgson, Sita Bhella, Vishal Kukreti, Patrick Veit-Haibach
Journal: Clinical Nuclear Medicine (2024)

Purpose The aims of this study were to perform a comprehensive review and meta-analyses and to report pooled diagnostic results on CXCR4-targeted PET, particularly considering detection, visualization, and prognostication. Patients and Methods This study followed PRISMA-DTA. A systematic search was conducted on major medical literature databases up to March 1, 2024. The search strategy was designed to include CXCR4 PET studies in hematologic malignancies. A random-effects model combined sensitivity values derived from 2-by-2 contingency tables. Pooled means for SUV max were computed. Analyses were performed by R software. Results The initial search resulted in a total of 1428 studies. Ultimately, 18 were eligible for systematic review and meta-analytic calculations. Twelve studies (320 patients) included B-cell lymphoma. The pooled detection rate of CXCR4 PET was 99.4% (95% confidence interval [CI]: 88.3%–100%). Marginal zone lymphoma was investigated in 5 studies (209 patients), with a pooled sensitivity of 97.6% (95% CI: 79.7%–99.8%). In studies on central nervous system lymphoma, CXCR4 PET demonstrated 100% accuracy at both patient and lesion levels. Also, it demonstrated a significantly higher tumor-to-background ratio than 18 F-FDG PET. For multiple myeloma, 5 studies (116 patients) showed a patient-level pooled sensitivity of 77.8% (95% CI: 64.4%–87.2%), whereas 18 F-FDG PET had 65.0% (95% CI: 55.2%–73.7%). The pooled SUV max for CXCR4 PET was 13.6 (95% CI: 9.3–17.8) versus 9.0 (95% CI: 6.3–11.7) for 18 F-FDG PET. Additionally, CXCR4 PET-derived parameters were significant predictors of survival in multiple myeloma. Conclusions CXCR4 PET can be a helpful imaging tool for evaluating hematologic malignancies, particularly in B-cell lymphoma and multiple myeloma patients. In specific clinical scenarios, it appears to be superior compared with the current standard-of-care imaging.
Maternal Exposure to Per- and Polyfluoroalkyl Substances and Offspring Chromosomal Abnormalities: The Japan Environment and Children’s Study
Authors: Kohei Hasegawa, Noriko Motoki, Yuji Inaba, Hirokazu Toubou, Takumi Shibazaki, Shoji F. Nakayama, Michihiro Kamijima, Teruomi Tsukahara, Tetsuo Nomiyama
Journal: Environmental Health Perspectives (2024)

Although recent
Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency
Authors: Haoming Wang, John W Vant, Andrew Zhang, Richard G Sanchez, Youjun Wu, Mary L Micou, Vincent Luczak, Zachary Whiddon, Natasha M Carlson, Seungyoon B Yu, Mirna Jabbo, Seokjun Yoon, Ahmed A Abushawish, Majid Ghassemian, Takeya Masubuchi, Quan Gan, Shigeki Watanabe, Eric R Griffis, Marc Hammarlund, Abhishek Singharoy, Gulcin Pekkurnaz
Journal: Nature Metabolism (2024)
An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms
Authors: Wenbo Sun, Tingyu Yang, Fengming Sun, Panhong Liu, Ji Gao, Xianmei Lan, Wei Xu, Yuhong Pang, Tong Li, Cuifeng Li, Qingtai Liang, Haoze Chen, Xiaohang Liu, Wenting Tan, Huanhuan Zhu, Fang Wang, Fanjun Cheng, Weiwei Zhai, Han-Na Kim, Jingren Zhang, Linqi Zhang, Lu Lu, Qiaoran Xi, Guohong Deng, Yanyi Huang, Xin Jin, Xiangjun Chen, Wanli Liu
Journal: Nature Immunology (2024)
Belantamab mafodotin, pomalidomide, and dexamethasone for triple class exposed/refractory relapsed multiple myeloma: a subgroup analysis of the ALGONQUIN trial
Authors: Arleigh McCurdy, Donna Reece, Martha L Louzada, Darrell White, Stephen Parkin, Michael P Chu, Rami Kotb, Hira Mian, Ibraheem Othman, Jiandong Su, Aniba Khan, Engin Gul, Suzanne Trudel
Journal: Blood Cancer Journal (2024)
Correction to “Protecting infants against RSV disease: an impact and cost-effectiveness comparison of long-acting monoclonal antibodies and maternal vaccination” [The Lancet Regional Health – Europe 38 (2024) 100829]
Authors: David Hodgson, Neil Wilkins, Edwin van Leeuwen, Conall H Watson, Jonathan Crofts, Stefan Flasche, Mark Jit, Katherine E Atkins
Journal: The Lancet Regional Health - Europe (2024)
Correction: Prostate cancer-associated SPOP mutations enhance cancer cell survival and docetaxel resistance by upregulating Caprin1-dependent stress granule assembly
Authors: Qing Shi, Yasheng Zhu, Jian Ma, Kun Chang, Dongling Ding, Yang Bai, Kun Gao, Pingzhao Zhang, Ren Mo, Kai Feng, Xiaying Zhao, Liang Zhang, Huiru Sun, Dongyue Jiao, Yingji Chen, Yinghao Sun, Shi-Min Zhao, Haojie Huang, Yao Li, Shancheng Ren, Chenji Wang
Journal: Molecular Cancer (2024)
Adenoid cystic carcinoma: insights from molecular characterization and therapeutic advances
Authors: Yunxuan Jia, Yupeng Liu, Haitang Yang, Feng Yao
Journal: MedComm (2024)

Abstract Adenoid cystic carcinoma (ACC) is a malignant tumor primarily originating from the salivary glands, capable of affecting multiple organs. Although ACC typically exhibits slow growth, it is notorious for its propensity for neural invasion, local recurrence, and distant metastasis, making it a particularly challenging cancer to treat. The complexity of ACC's histological and molecular features poses significant challenges to current treatment modalities, which often show limited effectiveness. Recent advancements in single‐cell RNA‐sequencing (scRNA‐seq) have begun to unravel unprecedented insights into the heterogeneity and subpopulation diversity within ACC, revealing distinct cellular phenotypes and origins. This review delves into the intricate pathological and molecular characteristics of ACC, focusing on recent therapeutic advancements. We particularly emphasize the insights gained from scRNA‐seq studies that shed light on the cellular landscape of ACC, underscoring its heterogeneity and pathobiology. Moreover, by integrating analyses from public databases, this review proposes novel perspectives for advancing treatment strategies in ACC. This review contributes to the academic understanding of ACC by proposing novel therapeutic approaches informed by cutting‐edge molecular insights, paving the way for more effective, personalized therapeutic approaches for this challenging malignancy.
Loss‐of‐function variants in RNA binding motif protein X‐linked induce neuronal defects contributing to amyotrophic lateral sclerosis pathogenesis
Authors: Di He, Xinyi He, Dongchao Shen, Liyang Liu, Xunzhe Yang, Meng Hao, Yi Wang, Yi Li, Qing Liu, Mingsheng Liu, Jiucun Wang, Xue Zhang, Liying Cui
Journal: MedComm (2024)

Abstract Despite being one of the most prevalent RNA modifications, the role of N6‐methyladenosine (m6A) in amyotrophic lateral sclerosis (ALS) remains ambiguous. In this investigation, we explore the contribution of genetic defects of m6A‐related genes to ALS pathogenesis. We scrutinized the mutation landscape of m6A genes through a comprehensive analysis of whole‐exome sequencing cohorts, encompassing 508 ALS patients and 1660 population‐matched controls. Our findings reveal a noteworthy enrichment of RNA binding motif protein X‐linked ( RBMX ) variants among ALS patients, with a significant correlation between pathogenic m6A variants and adverse clinical outcomes. Furthermore, Rbmx knockdown in NSC‐34 cells overexpressing mutant TDP43 Q331K results in cell death mediated by an augmented p53 response. Similarly, RBMX knockdown in ALS motor neurons derived from induced pluripotent stem cells (iPSCs) manifests morphological defects and activation of the p53 pathway. Transcriptional analysis using publicly available single‐cell sequencing data from the primary motor cortex indicates that RBMX‐regulated genes selectively influence excitatory neurons and exhibit enrichment in ALS‐implicated pathways. Through integrated analyses, our study underscores the emerging roles played by RBMX in ALS, suggesting a potential nexus between the disease and dysregulated m6A‐mediated mRNA metabolism.
Krüppel‐like factors family in health and disease
Authors: Tingwen Xiang, Chuan Yang, Zihan Deng, Dong Sun, Fei Luo, Yueqi Chen
Journal: MedComm (2024)

Abstract Krüppel‐like factors (KLFs) are a family of basic transcription factors with three conserved Cys2/His2 zinc finger domains located in their C‐terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation of KLFs is associated with a range of diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, and neurodegenerative diseases. Their multidimensional roles in modulating critical pathways underscore the significance in both physiological and pathological contexts. Recent research also emphasizes their crucial involvement and complex interplay in the skeletal system. Despite the substantial progress in understanding KLFs and their roles in various cellular processes, several research gaps remain. Here, we elucidated the multifaceted capabilities of KLFs on body health and diseases via various compliable signaling pathways. The associations between KLFs and cellular energy metabolism and epigenetic modification during bone reconstruction have also been summarized. This review helps us better understand the coupling effects and their pivotal functions in multiple systems and detailed mechanisms of bone remodeling and develop potential therapeutic strategies for the clinical treatment of pathological diseases by targeting the KLF family.
Executive Summary of the American Radium Society® (ARS) Appropriate Use Criteria (AUC) for Non-Small Cell Lung Cancer in a Central/Ultra-Central Location: Systematic Review and Guidelines
Authors: Henry S Park, Andreas Rimner, Arya Amini, Joe Y Chang, Stephen G Chun, Jessica Donington, Martin J Edelman, Matthew A Gubens, Kristin A Higgins, Puneeth Iyengar, Aditya Juloori, Benjamin Movsas, Zsuzsanna Nemeth, Matthew S Ning, George Rodrigues, Andrea Wolf, Charles B Simone
Journal: Journal of Thoracic Oncology (2024)
Hypoxia-Responsive Micelles Deprive Cofactor of Stearoyl-CoA Desaturase-1 and Sensitize Ferroptotic Ovarian Cancer Therapy
Authors: Jiajia Luo, Yaqi Shang, Ning Zhao, Xiaoying Lu, Zheng Wang, Xin Li, Xuan Meng, Yanjun Zhao
Journal: Biomaterials (2024)
Outcome after short exposure to tyrosine kinase inhibitors in pregnant female patients with chronic myeloid leukemia
Authors: Yingling Zu, Huifang Zhao, Jianling Chen, Huibing Dang, Yanrong Shi, Lixin Liang, Shuhao Mei, Yongping Song, Yanli Zhang
Journal: Journal of Hematology & Oncology (2024)
Polarization of circulating Follicular Helper T cells correlates with the severity of Bullous Pemphigoid
Authors: Corine Pérals, Sébastien le Jan, Céline Muller, Richard Le Naour, Philippe Bernard, Manuelle Viguier, Nicolas Fazilleau
Journal: British Journal of Dermatology (2024)

Follicular helper T (Tfh) cells form a distinct population of T-helper cells with different polarizations (type 1, type 2 and type 17) that regulates humoral responses and may participate in the pathophysiology of B-cell-mediated autoimmune diseases such as bullous pemphigoid (BP), a dermatosis mediated by autoantibodies specific for hemi-desmosomal proteins. To evaluate the impact on circulating Tfh cells of super potent topical corticosteroid (TCS) treatment, which is more effective and safer than high doses of oral corticosteroids, and is the recommended first-line treatment of BP. Using flow cytometry, we compared the frequency, polarization and activation of Tfh cells in the blood of patients with BP with age- and sex-matched control participants without BP at baseline and longitudinally, after the initiation of TCS treatment. We found that, at baseline, circulating Tfh cells were more frequent in patients with BP than in participants without BP and exhibited an activated phenotype. We further showed a decrease in type 1 and an increase in type 17 Tfh cells in the blood of patients with BP, which resulted in a higher type 2 + type 17 to type 1 Tfh cell ratio. This ratio correlated positively with disease severity, as measured by the Bullous Pemphigoid Disease Area Index. Remarkably, with TCS treatment, although the frequency of Tfh cells in patients with BP returned to a level similar to that of control participants, the activated phenotype persisted. Interestingly, serum interleukin-21 levels and the Tfh cell subset ratio, similarly to disease activity and serum anti-BP180 and anti-BP230 autoantibodies, decreased with TCS treatment. Overall, our findings suggest the involvement Tfh cell polarization in the pathophysiology of BP and open the door to modulation of Tfh cell activity for treatment purposes.
Corrigendum to “The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials” [J Infect 89 (2024) 106187]
Authors: Kristoffer Grundtvig Skaarup, Mats Christian Højbjerg Lassen, Daniel Modin, Niklas Dyrby Johansen, Matthew M Loiacono, Rebecca C Harris, Jason K H Lee, Marine Dufournet, Orly Vardeny, Alexander Peikert, Brian Claggett, Scott D Solomon, Jens Ulrik Stæhr Jensen, Tor Biering-Sørensen
Journal: Journal of Infection (2024)
CYP1B1 Promotes PARPi-Resistance via Histone H1.4 Interaction and Increased Chromatin Accessibility in Ovarian Cancer
Authors: Yite Xue, Taotao Yin, Shuo Yuan, Lingfang Wang, Hui Lin, Tianzhe Jin, Ruiyi Xu, Jiaxin Gu, Shizhen Shen, Xiaojing Chen, Zhuoye Chen, Ni Sima, Lifeng Chen, Weiguo Lu, Xiao Li, Xiaodong Cheng, Hui Wang
Journal: Drug Resistance Updates (2024)
68Ga-FAPI Response Evaluation Pitfall in a Patient With Esophageal Cancer After Neoadjuvant Therapy
Authors: Huipan Liu, Yuhong Liu, Jianwen Zhang, Yue Chen
Journal: Clinical Nuclear Medicine (2024)

Abstract We report the 68 Ga-FAPI PET/CT findings of inflammatory changes and fibrosis in a 55-year-old woman with a history of esophageal cancer after neoadjuvant therapy, which needs to be differentiated from other esophageal diseases during evaluation.