tbuckley/cabot-search huggingface dataset:
AORTIC VALVE THROMBUS ASSOCIATED WITH LEFT ATRIAL VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION (LAVA-ECMO) WHILE ON BIVALIRUDIN
Authors: Felix Nguyen, Raef Fadel, Jennifer Ann Cowger, Hassan Nemeh, Mir Babar Basir
Journal: Journal of the American College of Cardiology (2025)
WHERE’S THE SHUNT? A CASE OF ACQUIRED GERBODE DEFECT AFTER SURGICAL AORTIC VALVE REPLACEMENT FOR BICUSPID AORTIC VALVE ENDOCARDITIS
Authors: Rachel Morris, Sheraz Hussain, Valentina Turbay Caballero, Shermeen Bashir Memon, Amir Naqvi, Muhyaldeen Dia, Paul Richard Silverman, Rashmi Raghuvir
Journal: Journal of the American College of Cardiology (2025)
A CASE OF BIOPROSTHETIC MITRAL VALVE THROMBOSIS RESULTING IN SEVERE STENOSIS THAT WAS COMPLICATED BY ACUTE AORTIC REGURGITATION AFTER MITRAL VALVE REPLACEMENT
Authors: Nawal Abdi, Obiageli Obiako, Lloyd H. Greene, Marc Pelletier, Anene Ukaigwe
Journal: Journal of the American College of Cardiology (2025)
330P: A comparison of tarlatamab with real-world physicians’ choice of therapies in patients with previously treated small cell lung cancer
Authors: U. Tapan, R. Takundwa, G. Sajeev, X. Chai, J. Wang, X. Pundole, M. Pastel, H. Yang, F. Dirnberger
Journal: Journal of Thoracic Oncology (2025)
333P: Safety and effectiveness of adebrelimab as second- or later-line treatment in extensive-stage small-cell lung cancer: A prospective, real-world study
Authors: X. Liu, J. Wen, L. Jiang, S. Xu, L. Meng, N.L. Zhai, Z. Shao, P. Wu, K. Zhao, L. Kong, J. Peng, X. Meng
Journal: Journal of Thoracic Oncology (2025)
332P: Updated phase II efficacy and safety results of BNT327/PM8002 combined with paclitaxel as second-line (2L) therapy in small cell lung cancer (SCLC)
Authors: Y. Cheng, Y. Luo, X. Meng, L. Sun, Y. Yao, J. Fang, P. Zhang, Z. Qin, Y. Wang, H.H. Hu, Y. Zhao
Journal: Journal of Thoracic Oncology (2025)
329P: Intracranial efficacy of YL201, a novel B7-H3-targeting antibody-drug conjugate (ADC), in patients (pts) with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)
Authors: H. Zhao, Y. Ma, X. Meng, L. Wu, Y. Fan, Y. Zheng, Z. Liu, Y. Ji, D. Lv, S. Luo, D. Sommerhalder, S. Fu, Y. Huang, Y. Yang, W. Fang, Y. Zhao, X. Zhang, S. Chin, T. Xue, L. Zhang
Journal: Journal of Thoracic Oncology (2025)
M28 family peptidase derived from <i>Peribacillus frigoritolerans</i> initiates trained immunity to prevent MRSA via the complosome-phosphatidylcholine axis
Authors: Cheng-Kai Zhou, Zhen-Zhen Liu, Zi-Ran Peng, Xue-Yue Luo, Xiao-Mei Zhang, Jian-Gang Zhang, Liang Zhang, Wei Chen, Yong-Jun Yang
Journal: Gut Microbes (2025)

Methicillin-resistant Staphylococcus aureus (MRSA) represents a major global health threat due to its resistance to conventional antibiotics. The commensal microbiota maintains a symbiotic relationship with the host, playing essential roles in metabolism, energy regulation, immune modulation, and pathogen control. Mammals harbor a wide range of commensal bacteria capable of producing unique metabolites with potential therapeutic properties. This study demonstrated that M28 family peptidase (M28), derived from commensal bacteria Peribacillus frigoritolerans (P. f), provided protective effects against MRSA-induced pneumonia. M28 enhanced the phagocytosis and bactericidal activity of macrophages by inducing trained immunity. RNA sequencing and metabolomic analyses identified the CFB-C3a-C3aR-HIF-1α axis-mediated phosphatidylcholine accumulation as the key mechanism for M28-induced trained immunity. Phosphatidylcholine, like M28, also induced trained immunity. To enhance M28-mediated therapeutic potential, it was encapsulated in liposomes (M28-LNPs), which exhibited superior immune-stimulating properties compared to M28 alone. In vivo experiments revealed that M28-LNPs significantly reduced bacterial loads and lung damage following MRSA infection, which also provided enhanced protection against Klebsiella pneumoniae and Candida albicans. We first confirmed a link between complement activation and trained immunity, offering valuable insights into the treatment and prevention of complement-related autoimmune diseases.
327P: Genetic alterations of circulating tumor cells (CTCs) isolated from liquid biopsies of small cell lung cancer (SCLC) at the time of diagnosis
Authors: L. Martinetti, M. Aubry, H. Lena, Y. Le Guen, T. Goter, U. Jarry, C. Ricordel, A. Chatziioannou, R. Pedeux
Journal: Journal of Thoracic Oncology (2025)
350P: Spatial and single-cell transcriptomics to characterize T/B cell immune structures and neighborhood stromal components associated to immunotherapy response in non-small cell lung cancer
Authors: N. Porciello, L. D’Ambrosio, G. Frisullo, V. Balzano, G. Campo, F. Di Modugno, B. Palermo, E. Gallo, F. Goeman, F. De Nicola, F.T. Gallina, L. Landi, F. Cappuzzo, P. Visca, M.M. Rosado, P. Nisticò
Journal: Journal of Thoracic Oncology (2025)
349P: An immune checkpoint inhibitor response score (ICIRS) for non-small cell lung cancer treatment
Authors: G. Suay Montagud, M. Benet, J. García Sanchez, D. Hervas, M. Piqueras, L. Cordón, J. Garde Noguera, N. Piera, J.J. Iranzo Barreira, M. De Julian Campayo, A. Sanchez Hernandez, D. Lorente, S. Mena, F.D.A. Aparisi Aparisi, J. Sandoval del Amor, O. Juan-Vidal, A. Lahoz Rodriguez
Journal: Journal of Thoracic Oncology (2025)
346P: Multi-omics approach to identify factors underlying antibiotics (ABX)-mediated immunosuppression in a prospective trial of cancer immunotherapy
Authors: C. Alves Costa Silva, M. Fidelle, A. Bonato, G. Vitali, Y. Hassani, E. Menu, D. Suissa, L. Belluomini, A. Reni, C. Flament, R. Birebent, B. Routy, B. Besse, S. Ranque, P.E. Fournier, J. Doré, D. Drubay, L. Zitvogel, L. Derosa
Journal: Journal of Thoracic Oncology (2025)
343TiP: Maintenance therapy with fuzuloparib plus adebrelimab for ES-SCLC after first-line induction with fuzuloparib plus adebrelimab and chemotherapy: A prospective, single-arm, phase II clinical study
Authors: H. Xu, L. Wu, X. Su, Y. Hao, H. Feng, J. Zhang
Journal: Journal of Thoracic Oncology (2025)
342TiP: The PESGA trial: A prospective, open-label, single-arm, phase II study to evaluate first line therapy for ES-SCLC patients, treated by induction carboplatin/etoposide/pembrolizumab followed by maintenance of pembrolizumab/ sacituzumab govitecan
Authors: L.C. Roisman, S. Mann, A. Basel, B.J. Krayim, G. Kornev, N. Asna, N. Peled
Journal: Journal of Thoracic Oncology (2025)
341P: Efficacy of tumor treating fields (TTFields) in preclinical models of small cell lung carcinoma (SCLC)
Authors: U. Weinberg, R. Engelman, L. Somri-Gannam, T. Borkum, R. Blatt, D. Gerasimova, S. Cahal, C. Tempel Brami, M. Shai, E. Dor-On, I. Tzchori, A. Haber, M. Giladi, Y. Palti
Journal: Journal of Thoracic Oncology (2025)
336P: Durvalumab (D) as consolidation therapy for limited-stage small-cell lung cancer (LS-SCLC): ADRIATIC China subgroup analysis
Authors: Y. Cheng, Q. Wang, J. Fang, A. Shi, L. Wu, S. Lu, Z. Zhu, Y. Liu, Q. Wang, H. Jiang, X. Li, M. Wang, Y. Chen, H. Lu, Y. Duan, R. Meng, Y. Yang, Y. Chen, Y.S. Olivo, S. Senan
Journal: Journal of Thoracic Oncology (2025)
334P: Outcomes according to dosimetric factors: A secondary analysis of CALGB 30610 (Alliance)/RTOG 0538 (NRG)
Authors: M.D. Mix, M.K. Farris, X. Wang, B. Jaszewski, G. Mao, N. Foster, G. Masters, F. Laurie, K. Smith, N.B. Razavian, R. Alden, R. Komaki, T. Stinchcombe, J.D. Bradley, E.E. Vokes, J. Bogart
Journal: Journal of Thoracic Oncology (2025)
355P: Effect of immunotherapy on the peripheral immunoscore of patients affected by non-small cell lung cancer long responders or fast progressors
Authors: N.L. Alessio, P. Michel, F. Agustoni, I.C. Chillico, H.R. Recalde, M.T. Frascino, G. Galli, S. Corallo, G.M. Stella, S.M.C. Borgetto, F. Rifaldi, I. Lanzetta, A. Tortorella, F. Mascaro, M. Festari, S. Angelicola, F. Gelsomino, P. Pedrazzoli, A. Palladini
Journal: Journal of Thoracic Oncology (2025)
357P: Association of TROP2 quantitative continuous scoring (QCS) normalised membrane ratio (NMR) with efficacy in Chinese patients (pts) with advanced/metastatic non-small cell lung cancer (a/mNSCLC) treated with datopotamab deruxtecan (Dato-DXd) in TROPION-PanTumor02
Authors: Y-L. Wu, Z. Xiao, J. Li, J. Long, W. Li, Y. Cheng, H. Tu, X. Lin, Y. Wang, J. Zhao, Y. Chen, R. Ma, Y. Chen, M. Lu, B. Zhang, D. Carroll, J. Harper, D. Vonficht, H. Hu, Y. Sun
Journal: Journal of Thoracic Oncology (2025)
352P: Biomarkers of immunotherapy response in non-small cell lung cancer: Microbiota and short-chain fatty acids
Authors: A. Moratiel Pellitero, M. Zapata García, A. Goas Gomez, M. Martí-Pi, M. Gascon Ruiz, A. Sesma Goñi, A. RomeroMonleon, K.A. Osorio, M. Arribas Velasco, S. Esteras Per, R. Lastra, M.D. Isla Casado
Journal: Journal of Thoracic Oncology (2025)
353P: Gene expression analysis of PD-1 and PD-L1 in peripheral blood mononuclear cells (PBMCs) in non-small cell lung cancer (NSCLC) patients: Association with KRAS mutation status and patient outcomes
Authors: S. Agelaki, K. Michaelidou, V. Vagiatis, C. Koutoulaki, A. Koutsopoulos, A. Boukouris, A. Kyriakidou, M.A. Papadaki, L. Vamvakas, D. Mavroudis
Journal: Journal of Thoracic Oncology (2025)
354P: Monocyte subpopulations and circulating myeloid-derived suppressor cells as predictive biomarkers in advanced non-small cell lung cancer treated with ICIs
Authors: F. Biello, F. Vezzoli, G. Cognolato, G. Borra, S. Genestroni, C. Branni, J. Gennari, V. Martini, L. Negrini, G. Di Foggia, G. Genovese, S. Gobbato, R. Ben Ayed, A. Sica, A. Gennari
Journal: Journal of Thoracic Oncology (2025)
360P: Lymphocyte activation gene-3 (LAG-3) and cluster of differentiation-155 (CD-155) expression by immunohistochemistry do not predict response and survival in non-small lung cancer (NSCLC) patients treated with second-line nivolumab treatment
Authors: A.E. Apaydin Rollas, M. Erman, S.C. Onder
Journal: Journal of Thoracic Oncology (2025)
Discrete genetic subtypes and tumor microenvironment signatures correlate with peripheral T-cell lymphoma outcomes
Authors: Yasuhito Suehara, Kana Sakamoto, Manabu Fujisawa, Kota Fukumoto, Yoshiaki Abe, Kenichi Makishima, Sakurako Suma, Tatsuhiro Sakamoto, Keiichiro Hattori, Takeshi Sugio, Koji Kato, Koichi Akashi, Kosei Matsue, Kentaro Narita, Kengo Takeuchi, Joaquim Carreras, Naoya Nakamura, Kenichi Chiba, Yuichi Shiraishi, Satoru Miyano, Seishi Ogawa, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Journal: Leukemia (2025)

Abstract Peripheral T-cell lymphoma (PTCL) exhibits a diverse clinical spectrum, necessitating methods to categorize patients based on genomic abnormalities or tumor microenvironment (TME) profiles. We conducted an integrative multiomics study in 129 PTCL patients, performing whole-exome sequencing and identifying three genetic subtypes: C1, C2, and C3. C2 was characterized by loss of tumor suppressor genes and chromosomal instability, while C1 and C3 shared T follicular helper (TFH)-related genomic alterations, with C3 also showing a high incidence of IDH2 mutations and chromosome 5 gain. Compared to C1, survival was significantly worse in C2 (HR 2.52; 95% CI, 1.37–4.63) and C3 (HR 2.14; 95% CI, 1.17–3.89). We also estimated the proportions of immune cell fractions from the bulk RNA sequencing data using CIBERSORTx and classified TME signatures into the following hierarchical clusters: TME1 (characterized by increased B and TFH cells), TME2 (macrophages), and TME3 (activated mast cells). TME2 was associated with shorter survival (HR 3.4; 95% CI, 1.6–7.5) and was more frequent in C2 (64.3%) than in C1 (7.7%), whereas C1 had more TME3 signatures (80.8% vs. 28.6%). These findings highlight a significant relationship between genetic subtypes and TME signatures in PTCL, with important implications for clinical prognosis.
Zanubrutinib in Bing Neel syndrome: efficacy and tolerability
Authors: Anne-Marie L. Becking, Johannes P. M. van de Mortel, Oliver Tomkins, Thijs W. H. Flinsenberg, Nicole Japzon, Marie José Kersten, Jahanzaib Khwaja, Saskia Kuipers, Henriette Levenga, Sean McKeague, Stephen Opat, Ross T. Salvaris, Sherif Seif, Sheeba K. Thomas, Alexander F. J. E. Vrancken, Shirley D’Sa, Monique C. Minnema, Josephine M. I. Vos
Journal: Leukemia (2025)
363P: Retrospective evaluation of biomarkers (KRAS, TP53, STK11, KEAP1, POLE, PIK3CA and ARID1A) in pts with mNSCLC undergoing ICI mono or in combination with chemotherapy
Authors: J. Roeper, M. Falk, L.C. Heukamp, F. Griesinger
Journal: Journal of Thoracic Oncology (2025)
362P: LIPI score in advanced NSCLC treated with ICIs: Prognostic impact and blood immune-inflammatory correlations
Authors: M. Manini, F. Pecci, G. Mazzaschi, A. Dodi, P. Tamarozzi, M. Peroni, S. D’Agnelli, M. Pluchino, M. Verzè, R. Minari, F. Perrone, P. Bordi, A. Leonetti, S. Buti, N. Sverzellati, M. Tiseo
Journal: Journal of Thoracic Oncology (2025)
366P: Tumor derived exosomes in mediating cross-talk between PBMCs and EGFR mutant NSCLC cells and their role in osimertinib resistance
Authors: L. Amato, C. De Rosa, V. De Rosa, H.H. Sheikhhossein, A. Ariano, P. Franco, V. Nele, S. Capaldo, G. De Rosa, C. Tuccillo, F. Ciardiello, F. Morgillo, V. Tirino, C.M. Della Corte, F. Iommelli
Journal: Journal of Thoracic Oncology (2025)
368P: Molecular diagnosis of lung cancer via ctDNA and ctRNA detection on bronchoscopic fluid: A bicenter prospective study (BiLiBro)
Authors: G. Danino, A. Perrier, J. Camuset, V. Trosini-Desert, C. Mahiat, M. Teulier, J. Slomka, Y. Bouznad, A. Canellas, C. Meteye, P. Wang, J. Calvani, F. Coulet, E. Guillerm, J. Cadranel, V. Fallet
Journal: Journal of Thoracic Oncology (2025)
364P: Relationship of LIPI index and C-reactive protein with survival in a cohort of patients with advanced non-small cell lung carcinoma (NSCLC) treated with immunotherapy
Authors: R. Manjon Gomez, V. Serrano Pecos, M. Gonzalez Cordero, C. Garcia Macias, C. Bernabeu Cifuentes, A. Puertas Espada, M. Iciarra Garcia
Journal: Journal of Thoracic Oncology (2025)
369P: Biological correlates of cell free DNA (cfDNA) tumor fraction (TF) in advanced NSCLC
Authors: F.G. Dall’Olio, W.S. Zrafi, D. Vasseur, G. Jardali, L. Lawrance, N. Pata-Merci, M. Kind, N. Bourdonnec, R. Barbe, F. Barlesi, L. Lacroix, N. Lassau, A. Italiano, B. Besse
Journal: Journal of Thoracic Oncology (2025)
367P: Clinical characteristics and ctDNA as prognostic tools in KRAS-mutated NSCLC during first line treatment (1L)
Authors: P. Espinosa-Olarte, E. Munera Maravilla, P.J. Gomez Garcia, A. Blasco Cordellat, S. Torres Martinez, S. Calabuig Fariñas, L. Navarro-Cerveró, A. Navarro, A. Fernandez Díaz, C. Ferriol Martinez, E. Jantus Lewintre, C. Caballero Diaz
Journal: Journal of Thoracic Oncology (2025)
Cancer neuroscience in head and neck: interactions, modulation, and therapeutic strategies
Authors: Hanrui Wang, Xiaoyu Song, Hui Shen, Wanchen Liu, Yao Wang, Mingjun Zhang, Ting Yang, Yakui Mou, Chao Ren, Xicheng Song
Journal: Molecular Cancer (2025)

Head and neck cancer (HNC) is an aggressive malignancy with significant effects on the innervation. Not only is it at the top of the cancer spectrum with a dismal prognosis, but it also imposes considerable stress on patients and society owing to frequent neurological symptoms. With progress in cancer neuroscience, the interactions between HNC and the nervous system, as well as the underlying mechanisms, have become increasingly clear. Compelling evidence suggests communication of information between cancer and nerve cells and devastation of the neurological system with tumor growth. However, the thorough grasp of HNC in cancer neuroscience has been severely constrained by the intricacy of HNC and fragmented research. This review comprehensively organizes and summarizes the latest research on the crosstalk between HNC and the nervous system. It aims to clarify various aspects of the neurological system in HNC, including the physiology, progression, and treatment of cancer. Furthermore, the opportunities and challenges of cancer neuroscience in HNC are discussed, which offers fresh perspectives on the neurological aspects of HNC diagnosis and management.
383P: KRAS G12C vs. non-G12C non-small cell lung cancer (NSCLC): Insights from gene expression analysis
Authors: L. Masfarre Pinto, S. Clave, I. Sánchez, J. Perera-Bel, P. Berenguer-Molins, M. Bódalo-Torruella, N. Navarro-Gorro, C. Miquel, E. Torres, A. Taus Garcia, R. Del Rey-Vergara, B. Bellosillo Paricio, P.F. Simoes Da Rocha, E. Arriola Aperribay
Journal: Journal of Thoracic Oncology (2025)
Whole-genome sequencing of myeloproliferative neoplasms revealed dynamic clonal changes in the fibrotic or leukemic transformation and novel FOXP1 mutations in the fibrotic transformation
Authors: Hiroyuki Takamori, Ying-Jung Huang, Hidehito Fukushima, Kazuaki Yokoyama, Ting-Yu Huang, Ming-Chung Kuo, Seishi Ogawa, Yasuhito Nannya, Lee-Yung Shih
Journal: Leukemia (2025)
374P: Prognostic relevance of post-cycle 1 pembrolizumab levels in real-world NSCLC patients receiving first line IO or ChIO
Authors: C. Martinez, M. Molina Alejandre, V. Calvo De Juan, A. Collazo Lorduy, S. Vazquez Estevez, N. Fernandez Nunez, P. Diz Tain, M.L. Garrido Onecha, N. Martinez Banaclocha, E. Peña, M. Jiménez-Meseguer, A. Lopez Martin, S. Peña Cabia, S. Sequero Lopez, J. Rogado, A. Sanchez Hernandez, J. Coves Sarto, M.A. Sala Gonzalez, A. Cruz-Bermudez, M. Provencio Pulla
Journal: Journal of Thoracic Oncology (2025)
376P: Crosstalk between CAFs and cancer cells is mediated by hMENA-regulated secretory autophagy and affects immunotherapy response in NSCLC
Authors: A. Tocci, L. D’Ambrosio, N. Porciello, F. Di Modugno, A. Di Carlo, F.T. Gallina, R. Tajè, F. Paolini, V. Balzano, G. Campo, A.M. Mileo, P. Nisticò
Journal: Journal of Thoracic Oncology (2025)
Correction: SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway
Authors: Yi-Jun Shu, Hao Weng, Yuan-Yuan Ye, Yun-Ping Hu, Run-Fa Bao, Yang Cao, Xu-An Wang, Fei Zhang, Shan-Shan Xiang, Huai-Feng Li, Xiang-Song Wu, Mao-Lan Li, Lin Jiang, Wei Lu, Bao-San Han, Zhi-Gang Jie, Ying-Bin Liu
Journal: Molecular Cancer (2025)
Immune modulation to treat Alzheimer’s disease
Authors: Michael R. Duggan, David G. Morgan, Brittani R. Price, Binita Rajbanshi, Alfonso Martin-Peña, Malú Gámez Tansey, Keenan A. Walker
Journal: Molecular Neurodegeneration (2025)

Abstract Immune mechanisms play a fundamental role in Alzheimer’s disease (AD) pathogenesis, suggesting that approaches which target immune cells and immunologically relevant molecules can offer therapeutic opportunities beyond the recently approved amyloid beta monoclonal therapies. In this review, we provide an overview of immunomodulatory therapeutics in development, including their preclinical evidence and clinical trial results. Along with detailing immune processes involved in AD pathogenesis and highlighting how these mechanisms can be therapeutically targeted to modify disease progression, we summarize knowledge gained from previous trials of immune-based interventions, and provide a series of recommendations for the development of future immunomodulatory therapeutics to treat AD.
Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial
Authors: Marc P Bonaca, Andrei-Mircea Catarig, Kim Houlind, Bernhard Ludvik, Joakim Nordanstig, Chethana Kalmady Ramesh, Neda Rasouli, Harald Sourij, Alex Videmark, Subodh Verma
Journal: The Lancet (2025)
C1Q+ TPP1+ macrophages promote colon cancer progression through SETD8-driven p53 methylation
Authors: Veronica Veschi, Francesco Verona, Sebastiano Di Bella, Alice Turdo, Miriam Gaggianesi, Simone Di Franco, Laura Rosa Mangiapane, Chiara Modica, Melania Lo Iacono, Paola Bianca, Ornella Roberta Brancato, Caterina D’Accardo, Gaetana Porcelli, Vincenzo Luca Lentini, Isabella Sperduti, Elisabetta Sciacca, Peter Fitzgerald, David Lopez-Perez, Pierre Martine, Kate Brown, Giuseppe Giannini, Ettore Appella, Giorgio Stassi, Matilde Todaro
Journal: Molecular Cancer (2025)

In many tumors, the tumor suppressor TP53 is not mutated, but functionally inactivated. However, mechanisms underlying p53 functional inactivation remain poorly understood. SETD8 is the sole enzyme known to mono-methylate p53 on lysine 382 (p53K382me1), resulting in the inhibition of its pro-apoptotic and growth-arresting functions. We analyzed SETD8 and p53K382me1 expression in clinical colorectal cancer (CRC) and inflammatory bowel disease (IBD) samples. Histopathological examinations, RNA sequencing, ChIP assay and preclinical in vivo CRC models, were used to assess the functional role of p53 inactivation in tumor cells and immune cell infiltration. By integrating bulk RNAseq and scRNAseq approaches in CRC patients, SETD8-mediated p53 regulation resulted the most significantly enriched pathway. p53K382me1 expression was confined to colorectal cancer stem cells (CR-CSCs) and C1Q+ TPP1+ tumor-associated macrophages (TAMs) in CRC patient tissues, with high levels predicting decreased survival probability. TAMs promote p53 functional inactivation in CR-CSCs through IL-6 and MCP-1 secretion and increased levels of CEBPD, which directly binds SETD8 promoter thus enhancing its transcription. The direct binding of C1Q present on macrophages and C1Q receptor (C1QR) present on cancer stem cells mediates the cross-talk between the two cell compartments. As monotherapy, SETD8 genetic and pharmacological (UNC0379) inhibition affects the tumor growth and metastasis formation in CRC mouse avatars, with enhanced effects observed when combined with IL-6 receptor targeting. These findings suggest that p53K382me1 may be an early step in tumor initiation, especially in inflammation-induced CRC, and could serve as a functional biomarker and therapeutic target in adjuvant setting for advanced CRCs.
Senescence profiling of monoclonal gammopathies reveals paracrine senescence as a crucial defense against disease progression
Authors: Gabriel Alvares Borges, Marta Diaz-delCastillo, Angelo J. Guilatco, Bilal Mohamad El-Masri, Fatima A. Mustapha, Michael T. Gundesen, Maja Hinge, Thomas Lund, Nadine Abdallah, Linda B. Baughn, Ming Xu, Anne Gingery, Tamar Tchkonia, James L. Kirkland, Taxiarchis Kourelis, Matthew T. Drake, Thomas Levin Andersen, Megan M. Weivoda
Journal: Leukemia (2025)

Multiple myeloma (MM) is a plasma cell (PC) malignancy that is preceded by monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple myeloma (SMM). MGUS and SMM PCs exhibit the same primary oncogenic abnormalities as MM but lack the end-organ damage that defines proliferative disease, suggesting that clonal PCs in these precursor conditions could exhibit senescence or senescence-like growth arrest. Herein we identified monoclonal gammopathy patient-derived PCs that exhibit senescence features and found that senescent PCs were significantly increased in MGUS patients compared to SMM or MM. Spatial analysis of senescent PCs in stable MGUS and SMM patient biopsies demonstrated the activation of local paracrine senescence in the bone marrow microenvironment. Stable MGUS and SMM patients also exhibited disease-specific senescence-associated secretory phenotype (SASP) signatures that significantly correlated with PC burden and clonal antibody. In contrast, progressing MGUS, SMM, and new MM patients lacked local paracrine senescence responses and robust activation of disease specific SASP signatures. Overall, these data suggest that failure to activate tumor-specific paracrine senescence responses is key to disease progression in monoclonal gammopathies.
385P: KRAS-dependent and independent impact of STK11 mutations in NSCLC: Clinical characteristics
Authors: N. Wagener, A. Rasokat, D. Nur Türkmen, Y.S. Park, D. Schinol, F. John, L.V. Ruge, M. Verheyen, H. Scharpenseel, S. Michels, R. Riedel, R.N. Fischer, A. Kron, A. Rothe, J-P. Weber, R. Büttner, S. Merkelbach-Bruse, U. Siebolts, J. Wolf, M. Scheffler
Journal: Journal of Thoracic Oncology (2025)