tbuckley/cabot-search huggingface dataset:
The intricate role of adipokines in cancer-related signaling and the tumor microenvironment: Insights for future research
Authors: Dimitris Kounatidis, Natalia G Vallianou, Irene Karampela, Evgenia Grivakou, Maria Dalamaga
Journal: Seminars in Cancer Biology (2025)

Obesity represents a global health challenge, with adipose tissue acting as a highly active endocrine organ that synthesizes and secretes a diverse array of bioactive proteins, known as adipokines. These cell signaling molecules regulate metabolic equilibrium, inflammatory cascades, and immune surveillance, exerting substantial systemic effects. A growing body of evidence has also highlighted their key role in cancer biology, through their intricate impact on oncogenic signaling networks and the tumor microenvironment (TME). The TME, a highly dynamic and heterotypic network composed of malignant cells, infiltrating immune cells, stromal constituents, and extracellular matrix elements, facilitates tumor evolution and immune evasion. Among adipokines, adiponectin and leptin have been extensively studied. Research has shown that adiponectin exhibits tumor-suppressive properties, whereas leptin enhances proliferative, angiogenic, and inflammatory pathways that promote malignancy. However, these effects are context-dependent and, at times, contradictory across different studies. Furthermore, the functional landscape of adipokines in cancer extends beyond these paradigms, with emerging research identifying a broader spectrum of novel adipokines involved in cancer reprogramming. This review delineates the molecular interplay between adipokines and oncogenic pathways, elucidating their mechanistic contributions to TME crosstalk and immune modulation. Additionally, we examine their potential as diagnostic and prognostic biomarkers and assess their viability as therapeutic targets for precision oncology. By integrating current evidence and identifying unresolved questions, this review aims to refine our understanding of adipokine-driven tumor biology and establish a platform for future research.
Onboard, tethered IL-12 boosts potency of the Tmod NOT gate and preserves selectivity
Authors: Jingli A Zhang, Sara Imboden, Dongwoo Lee, Alexandre Zampieri, Sanam Shafaattalab, Jushen Liang, Richele Bruno, Jon Torres, Alexander Partin, Mark E Daris, Timothy P Riley, Alexander Kamb
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background To reach their full potential in cancer therapy, immune cells engineered with synthetic constructs must achieve the challenging dual objectives of potency and selectivity to overcome the key obstacle: non-specific cytotoxicity. These problems are especially challenging for solid tumor therapy, where antigen tissue specificity, accessibility, and tumor microenvironment are problematic. Cells engineered with receptors that act as synthetic logic gates promise to address the issue of tumor specificity by targeting antigen profiles rather than single antigens. Nevertheless, there are limits to the potency benefit that can be achieved at the level of the antigen-targeting receptors. One approach to enhance potency beyond the acute sensitivity of receptor activation is to co-opt a major source of ancillary stimulation in the normal immune response, cytokine receptors. Methods Enhancing CAR-T efficacy with engineered onboard cytokines, often referred to as “armoring”, is one such approach to boost potency. However, such constructs run the risk of overriding tumor selectivity and eroding the therapeutic window. Here we design and test onboard cytokine constructs that enhance potency and preserve selectivity of a synthetic NOT logic gate construct called Tmod, potentially addressing some of the major challenges in oncology in a single synthetic design. Results We focused especially on a module encoding membrane-tethered interleukin (IL)-12, a construct that significantly enhances Tmod antigen-dependent long-term proliferation and potency both in vitro and in vivo, without compromising the NOT gate selectivity. Notably, three substantially different in vivo models, including one that employs mouse surrogate antigens, were used to assess preclinical dose-dependent efficacy and safety. Together, these studies make a strong case for the robustness of the design. Conclusions We conclude that the mem-IL-12 module can be combined with multiple Tmod constructs to boost efficacy and persistence while preserving the on-tumor selectivity.
Engineered<i>Mycobacterium smegmatis</i>expressing anti-PD-L1/IL-15 immunocytokine induces and activates specific antitumor immunity
Authors: Yi Mei, Junmeng Zhu, Jie Shao, Lin Li, Fangcen Liu, Xiaoxuan Sha, Yang Yang, Jie Shen, Rutian Li, Baorui Liu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors and cytokines have revolutionized tumor treatment but are still limited by dose-dependent toxicity and efficacy. In situ vaccine platforms based on intelligent microbes are promising therapeutic strategies that sustainably deliver drugs locally without causing severe systemic risks. Methods In this study, we have innovatively engineered a non-pathogenic, adjuvant-acting Mycobacterium smegmatis ( M. smegmatis ) that co-expresses a programmed cell death-ligand 1 (PD-L1) inhibitor and an interleukin-15 (IL-15) cytokine complex containing the interleukin-15 receptor alpha (IL-15Rα) sushi domain (Ms-PDL1scfv-IL15). Results We demonstrate that the fusion protein of PD-L1 inhibitor and IL-15 cytokine systemically binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. The bifunctional Ms-PDL1scfv-IL15 overcomes resistance to PD-L1 blockade, recruits numerous immune cells in situ, induces dendritic cells (DCs) maturation, initiates the M1 antitumor polarization of macrophages, increases the proliferation and activation of natural killer cells and tumor-infiltrating CD8 + T cells, inhibits regulatory T cells, elicits abscopal effects, stimulates rapid tumor regression, prevents metastasis, and leads to long-term survival in several syngeneic tumor mouse models. We also found that the combination of Ms-PDL1scfv-IL15 with granulocyte-macrophage colony-stimulating factor (GM-CSF) synergistically stunted the tumor progress and stasis. Moreover, intratumoral administration of Ms-PDL1scfv-IL15 can capture tumor antigen fragments, and boost DCs presentation of antigens, which remarkably initiates tumor antigen-specific immune response, leading to durable tumor regression and specific antitumor immunity. Conclusion In summary, the engineered M. smegmatis can recruit and activate innate and adaptive antitumor immune responses, offering a potent cancer immunotherapy strategy to treat patients with cold tumors or resistance to checkpoint blockade.
Development and validation of a serum proteomic test for predicting patient outcomes in advanced non-small cell lung cancer treated with atezolizumab or docetaxel
Authors: Minu K Srivastava, Wei Zou, Mark McCleland, Joanna Roder, Senait Asmellash, Patrick Norman, Lelia Net, Laura Maguire, Heinrich Roder, Robert Georgantas, David S Shames
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Programmed cell death-ligand 1 (PD-L1) expression is used in treatment decision-making for patients with advanced non-small cell lung cancer, determining if immune checkpoint inhibitors (ICI) are recommended. Patient selection for ICI treatment can be improved by incorporating the host response. We developed and carried out multiple independent validations of a blood-based test designed to stratify outcomes for patients treated with atezolizumab. Methods A mass spectrometry-based test was developed from a cohort of patients treated with atezolizumab and validated in two clinical trials (n=269, 823) comparing atezolizumab with docetaxel. The test classifies patients as Good or Poor indicating better or worse outcomes, respectively. The prognostic and predictive power of the test was assessed and evaluated within PD-L1 subgroups. Protein enrichment methods were used to investigate the association of test classification with biological processes. Results Approximately 50% of patients were assigned to each classification in all three cohorts. When treated with atezolizumab, the Good subgroup had superior outcomes in all cohorts. Overall survival (OS) HR (95% CI) for Good patients in each cohort was: 0.23 (0.12 to 0.44), 0.32 (0.21 to 0.51), and 0.52 (0.41 to 0.66) and persisted in all PD-L1 subgroups. The test was predictive of differential OS and progression-free survival in one cohort, but not in the other. Enrichment techniques indicated the test was associated with acute inflammatory response, acute phase response, and complement activation. Conclusions Aspects of host immune response to disease can be assessed from the circulating proteome and provide outcome stratification for patients treated with atezolizumab. Combining this information with PD-L1 measurements improves prediction of outcomes.
CAR-NK’s balancing act: when scFv affinity is not too tight, not too loose… but just right?
Authors: Yanling Liao, Mitchell S Cairo
Journal: Journal for ImmunoTherapy of Cancer (2025)

Chimeric antigen receptor (CAR) therapies have revolutionized cancer treatment by enabling immune cells to target tumor cells with high specificity. While extensive research has focused on optimizing single-chain variable fragment (scFv) affinity in CAR-T cells, its impact on CAR-natural killer (NK) cell function remains less understood. A recent study by Rahnama et al , published in the Journal for ImmunoTherapy of Cancer , addresses this gap by investigating how fine-tuning scFv affinity influences CAR-NK efficacy against acute myeloid leukemia. The study demonstrates that lower-affinity 7G3-based CAR-NK cells exhibit superior antigen discrimination, prolonged persistence, and enhanced tumor control compared with their high-affinity counterparts. However, findings with 26292-based CAR-NK cells reveal a more complex, context-dependent relationship between scFv affinity and cytotoxic function. These results highlight the need for individualized optimization of CAR designs, considering factors such as epitope accessibility, ligand-binding kinetics, and cellular context. Future studies incorporating real-time kinetic analyses and tumor microenvironment modeling will be crucial for refining CAR-NK therapies. Striking the right balance between binding affinity, dwell time, and serial killing capacity could enhance CAR-NK therapeutic potential while minimizing toxicity risks.
INBRX-106: a hexavalent OX40 agonist that drives superior antitumor responses via optimized receptor clustering
Authors: Nisha Holay, Rashi Yadav, Sae Jeong Ahn, Melissa J Kasiewicz, Anya Polovina, Annah S Rolig, Thi Staebler, Bryan Becklund, Noah D Simons, Yoshinobu Koguchi, Brendan P Eckelman, Yaiza Diaz de Durana, William L Redmond
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immunotherapies targeting immune checkpoint inhibitors have revolutionized cancer treatment but are limited by incomplete patient responses. Costimulatory agonists like OX40 (CD134), a tumor necrosis factor receptor family member critical for T-cell survival and differentiation, have shown preclinical promise but limited clinical success due to suboptimal receptor activation. Conventional bivalent OX40 agonists fail to induce the trimeric engagement required for optimal downstream signaling. To address this, we developed INBRX-106, a hexavalent OX40 agonist designed to enhance receptor clustering independently of Fc-mediated crosslinking and boost antitumor T-cell responses. Methods We assessed INBRX-106’s effects on receptor clustering, signal transduction, and T-cell activation using NF-kß reporter assays, confocal microscopy, flow cytometry, and single-cell RNA sequencing. Therapeutic efficacy was evaluated in murine tumor models and ex vivo human samples. Clinical samples from a phase I/II trial ( NCT04198766 ) were also analyzed for immune activation. Results INBRX-106 demonstrated superior receptor clustering and downstream signaling compared with bivalent agonists, leading to robust T-cell activation and proliferation. In murine models, hexavalent OX40 agonism resulted in significant tumor regression, enhanced survival, and increased CD8 + T-cell effector function. Clinical pharmacodynamic analysis in blood samples from patients treated with INBRX-106 showed heightened T-cell activation and proliferation, particularly in central and effector memory subsets, validating our preclinical findings. Conclusions Our data establish hexavalent INBRX-106 as a differentiated and more potent OX40 agonist, showcasing its ability to overcome the limitations of conventional bivalent therapies by inducing superior receptor clustering and multimeric engagement. This unique clustering mechanism amplifies OX40 signaling, driving robust T-cell activation, proliferation, and effector function in preclinical and clinical settings. These findings highlight the therapeutic potential of INBRX-106 and its capacity to redefine OX40-targeted immunotherapy, providing a compelling rationale for its further clinical development in combination with checkpoint inhibitors.
Role of Staphylococcus aureus Colonization in Burn Patients
Authors: Susanne Sütterlin, Marie Lindblad, Eva Tano, Sara Frosth, Filip Farnebo, Torgny Schennings, Jan-Ingmar Flock, Fredrik Huss
Journal: Journal of Infection (2025)

Staphylococcus aureus is an important pathogen in burn patients and contributes to mortality, however, the role of colonization with S. aureus in the course of the disease is less well described. The study aimed to determine the frequency of S. aureus colonization in 80 patients treated in a national burn centre in Uppsala, Sweden, during the first ten days of hospitalization in relation to length of stay, number of days before antibiotic treatment started and mortality; additionally, epidemiological relationship and phylogeny were analyzed. A total of 38/80 (47.5%) patients tested positive for S. aureus upon admission, while 47 out of 65 patients who completed the 10-day study period (72%), were colonized with S. aureus. Patients, that were colonized at admission tended to stay longer at the burn centre, particularly when admitted with more severe conditions corresponding to a rBaux score >70 (p=0.05, R2=0.09). Patients carrying isolates of phylogroup 2 received antibiotic treatment approximately one day later than patients with isolates belonging to phylogroup 1 (p<0.05, R2= 0.09). The study findings emphasize that screening for S. aureus colonization in burn patients upon admission, particularly in critically injured patients, could prove beneficial in optimizing antibiotic therapy.
Population-based longitudinal study over two decades of Candida and Candida-like species bloodstream infection reveals gender and species differences in mortality, recurrence and resistance
Authors: Adam G Stewart, Kevin B Laupland, Felicity Edwards, Sophia Koo, Sarah P Hammond, Patrick Na Harris, David L Paterson, Monica A Slavin, Sharon C-A Chen
Journal: Journal of Infection (2025)

The global burden of bloodstream infection (BSI) due to Candida, and species previously classed as Candida (Candida-like species) is substantial. Recent emergence of Candida auris, fluconazole-resistant Candida parapsilosis and echinocandin-resistant Nakaseomyces glabratus emphasize the importance of global and regional surveillance. Blood cultures with growth of Candida/Candida-like species in Queensland, Australia (population ≈ 5 million) over a 20-year period (1 January 2000-31 December 2019) were retrospectively identified. Clinical, microbiological and outcome information was obtained from state-wide databases. Cox proportional and Fine-Gray subdistribution hazard models were used to construct hazard ratios for 30-day all-cause case fatality and 1-year recurrence, respectively. A total of 2,586 episodes (2,420 patients) of Candida/Candida-like bloodstream infection (Ca-BSI) were identified; 249 episodes (9.5%) were in children. Candida albicans and C. parapsilosis complex reduced in frequency whilst N. glabratus and Candida dubliniensis increased during the study. Of 1,836 isolates tested, fluconazole (3.2%) and echinocandin (0.7%) resistance rates were low, with a decrease in fluconazole resistance observed from the first half of the study period to the latter half (4.5% versus 2.2%, P<0.01). Overall, 30-day all-cause mortality (21%) was unchanged: C. parapsilosis complex (aHR 0.44, 95% CI 0.32-0.60) was associated with decreased mortality, while C. tropicalis (aHR 1.35, 95% CI 0.95-1.93) was associated with an increase. Only 3.1% episodes demonstrated recurrence of Ca-BSI within one year. Presence of uncommon Candida species (aSHR 6.60, 95% CI 2.99-14.56) and an endovascular source of infection (aSHR 4.42, 95% CI 1.87-10.46) were associated with recurrence, while male gender (aSHR 0.57, 95% CI 0.35-0.92) was protective. Resistance to fluconazole (3.2% vs 3.5%, P=0.58) and echinocandins (0.6% vs 2.0%, P=0.05) were higher in recurrent Ca-BSI episodes. Females had a higher rate of fluconazole resistance (4.1% versus 2.4%, P=0.02). Our study highlights important shifts in causative species and resistance patterns of Ca-BSI which impacts clinical management. Antifungal resistance rates were low overall. The identification of new modifiable and non-modifiable risk factors for recurrence and mortality provides opportunities to examine new strategies to improve patient outcomes.
Clinical Trials for Hepatitis Delta Virus in the WHO African region: A neglected virus among neglected viruses
Authors: Marion Delphin, James Campbell, Eloi R Verrier, Motswedi Anderson, Gloria Sukali, Tongai Maponga, Alexander Stockdale, Philippa C Matthews
Journal: Journal of Infection (2025)

We set out to evaluate the extent to which Hepatitis Delta Virus (HDV) Clinical Trials (CT) include populations from the World Health Organisation (WHO) African region, aiming to highlight inequities and advocate for global investment in inclusive HDV research. We screened the clinicaltrial.gov and the WHO International Clinical Trials Registry Platform (ICTRP) repositories for 'Hepatitis Delta virus' and 'HDV' related CT. Datasets were merged using R v.4.2.1. We classified studies according to location and associated WHO region. We identified a total of 47 CT on HDV, mainly conducted in Europe (69.3%), Western Pacific (19.6%) and the Americas (8.5%). Despite the highest estimated anti-HDV seroprevalence in the general population, there were no CT registered in the WHO African region. CT are still predominantly done in the regions of initial drug discovery, as seen with bulevirtide (Europe) and lonafarnib (Americas). HDV-focused CT are needed in the WHO African region, as the region with the highest disease burden, and unique genotypes (5-8); to evaluate efficacy of novel anti-HDV compounds and to ensure that new treatments can be distributed and deployed as they become available.
Evaluation of the efficacy and safety of dapsone alone or associated with topical corticosteroids for pemphigus foliaceus: a retrospective multicenter study
Authors: Sofia Tzoumpa, Gérôme Bohelay, Saskia Ingen-Housz-Oro, Emmanuelle Tancrède-Bohin, Vanina Seta, Pascal Joly, Julie Bouteiller, Manuelle-Anne Viguier, Clémence Berthin, Olivier Dereure, Florian Lombart, Sophie Duvert-Lehembre, Nadège Cordel, Emmanuel Mahé, Irène Gallais-Sérézal, Géraldine Jeudy, Damien Boutin, Perrine Rousseau, Noémie Litrowski, Alexis Brue, Clémence Lepelletier, Marina Alexandre, Frédéric Caux, Catherine Prost, Christelle Le Roux-Villet
Journal: British Journal of Dermatology (2025)

This retrospective series is the largest one to date, with the longest follow-up, to study the efficacy and safety of dapsone in patients with pemphigus foliaceous (PF). The results of this study indicate that dapsone's long-term efficacy for PF is modest, whether used alone or in combination with topical corticosteroids, even for mild cases, and is associated with a high rate of AEs. Dapsone may still be appropriate for patients with mild PF who have contraindications to immunosuppressive therapies, in other situations, alternative systemic therapies, particularly rituximab, should be considered.
Tactical deception in cephalopods: a new framework for understanding cognition
Authors: Christian Drerup, Elias Garcia-Pelegrin, Clive Wilkins, James E Herbert-Read, Nicola S Clayton
Journal: Trends in Ecology & Evolution (2025)

Many animals rely on deception, including signalling misinformation, to gain advantages over others. While many deceptive strategies rely on deterministic patterns or conditioning, some taxa can flexibly adapt their deceptive behaviour to the identity, perspective, or inferred goals of the observer. These context-dependent deceptive strategies could be considered 'tactical deception' if they rely on higher-level cognitive processes to execute. Here, we outline why cephalopods, such as octopus and cuttlefish, are ideal candidates to explore the link between deception and cognition. As tactical deception relies on understanding differences in one's own and another observer's perspective, we suggest tactical deception as a framework to study aspects of cognition in other animals.
Plasminogen activation and plasmin activity are not required to prevent venous thrombosis/thromboembolism
Authors: Yaqiu Sang, Marzia Menegatti, Jennifer A Brody, Kerri L Wiggins, Brian C. Cooley, Katheryn Natalya Kapfer, Kadri Kangro, Bas de Laat, Flora Peyvandi, Matthew J. Flick, Nicholas Smith, Amy D. Shapiro, Alisa S. Wolberg
Journal: Blood (2025)
Type 2 calreticulin mutations activate ATF6 to promote BCL-xL-mediated survival in myeloproliferative neoplasms
Authors: Nicole S Arellano, William L Heaton, Mirielle C Nauman, Abigail E Runnels, Jacky Gomez-Villa, Daniele Vanni, Melissa Gaviria, Maihi Fujita, Nathan M Krah, Michele Ciboddo, Saveg Yadav, Callie T Brown, Parker D Bowden, Amy K Chen, Christopher Henning, Silvia Catricalà, Ilaria Carola Casetti, Oscar Borsani, Elisa Rumi, Daniela Pietra, Isabelle Plo, Caroline Marty, Marco Marchetti, Caner Saygin, Ami B Patel, Shannon E Elf
Journal: Blood (2025)
Ultrasensitive detection of circulating multiple myeloma cells by next-generation flow after immunomagnetic enrichment
Authors: Marta Lasa, Carmen Gonzalez, Laura Notarfranchi, Anastasiia Zherniakova, Diego Alignani, Leire Burgos, Maria José Calasanz, Paula Rodriguez-Otero, Jose J. Perez, Clara Gomez, Veronica Gonzalez-Calle, Felipe de Arriba, Luis Palomera Bernal, Miguel Angel Alvarez Rivas, Esther Clavero Sanchez, Enrique M. Ocio, Ana Pilar Gonzalez-Rodriguez, Sunil Lakhwani, Angela Ibañez, Albert Oriol, Anna Sureda, Laura Rosiñol, Christiane Siewert, Alberto Orfao, Juan-Jose Lahuerta, Joan Bladé, Maria-Victoria Mateos, Jesús F. San-Miguel, Maria-Teresa Cedena, Joaquin Martinez-Lopez, Noemi Puig, Bruno Paiva
Journal: Blood (2025)
NIR-responsive bio-system with sequential antibacterial and immunomodulatory effects for the treatment of periodontitis
Authors: Xinyi Qiu, Wanping Wang, Chenying Shen, Yue Zhao, Xiao Song, Yijun Yu, Chao Liu, Wenlei Wu, Leiying Miao, Shuangshuang Ren
Journal: Bioactive Materials (2025)
VPS9D1-AS1 antisense therapy via lipid nanoparticles reprograms cold tumors and enhances immunotherapy in colorectal cancer
Authors: Lei Yang, Zhen Li, Xiaoxi Huang, Lei Huang, Yangkai Fu, Baocheng Zhao, Yudong Zhang, Liangang Ma, Shuai Jing, Liyuan Fu, Dong Zhang, Hao Qu
Journal: Journal of Controlled Release (2025)
A randomized controlled trial of intravenous immunoglobulin vs standard of care for the treatment of chronic active antibody-mediated rejection in kidney transplant recipients
Authors: William R Mulley, Dhakshayini Tharmaraj, Kevan R Polkinghorne, Greg H Tesch, Sukhpal K Dayan, Edward Kwan, Moshe Olshansky, Tia Mark, Darren Lee, Peter F Mount, Germaine Wong, Kate R Wyburn, Wai H Lim, Peter G Kerr, David J Nikolic-Paterson, John Kanellis
Journal: Kidney International (2025)