tbuckley/cabot-search huggingface dataset:
Interferon-stimulated gene IFI27 as a multifaceted candidate target in precision medicine
Authors: Maryam Shojaei, Anthony S McLean
Journal: Trends in Immunology (2025)

IFI27, an interferon (IFN)-stimulated gene, is emerging as a crucial player in immune responses across various species, with significant implications for precision medicine. Commonly found among the most upregulated genes in infections, cancers, as well as inflammatory and autoimmune disorders, IFI27 is ready to be trialed in clinical practice for certain indications, and holds promise as an immunomodulatory target. We hypothesize that IFI27 plays a dual role, typically supporting immune defense but sometimes contributing to disease progression, which might render it a putative biomarker for diagnosis, prognosis, and treatment response. We advocate for focused research on IFI27 to unlock its potential in precision medicine and to contribute to a unifying framework of its mechanisms in the immune response. Our viewpoint is supported by numerous studies highlighting IFI27's involvement across various conditions and the possibilities for clinical application.
Proteomic Analysis of Plasma and Urine for Efficacy Prediction Biomarkers of JAK Inhibitors Combined with Phototherapy in Vitiligo
Authors: Zhonghui Hu, Shiyu Zhang, Lu Yang, Lu Lu, Jindi Feng, Huimin He, Jianqiang Wu, Li Wen, Yuehua Liu, Tao Wang
Journal: British Journal of Dermatology (2025)

The combination of Janus kinase (JAK) inhibitors and narrow-band ultraviolet B (NB-UVB) therapy is an effective treatment for vitiligo; however, reliable and convenient biomarkers for predicting treatment efficacy prior to therapy are currently lacking. The biomarker combination of pre-treatment plasma C-C motif chemokine ligand 5 and fibrinogen-like protein 1 levels, along with urine ezrin and glyceraldehyde 3-phosphate dehydrogenase levels, can predict the sensitivity to baricitinib combined with NB-UVB therapy in patients with vitiligo.
Central Nervous System Macrophages in Health and Disease
Authors: Hannah Van Hove, Donatella De Feo, Melanie Greter, Burkhard Becher
Journal: Annual Review of Immunology (2025)

The central nervous system (CNS) has a unique set of macrophages that seed the tissue early during embryonic development. Microglia reside in the parenchyma, and border-associated macrophages are present in border regions, including the meninges, perivascular spaces, and choroid plexus. CNS-resident macrophages support brain homeostasis during development and steady state. In the diseased brain, however, the immune landscape is altered, with phenotypic and transcriptional changes in resident macrophages and the invasion of blood-borne monocytes, which differentiate into monocyte-derived macrophages upon entering the CNS. In this review, we focus on the fate and function of the macrophage compartment in health, neurodegenerative conditions such as amyloidosis, and neuroinflammation as observed in multiple sclerosis and infection. We discuss our current understanding that monocyte-derived macrophages contribute to neuropathology whereas native macrophages play a neuroprotective role in disease.
The Interplay Between Innate Immunity and Nonimmune Cells in Lung Damage, Inflammation, and Repair
Authors: Chrysante S. Iliakis, Stefania Crotta, Andreas Wack
Journal: Annual Review of Immunology (2025)

As the site of gas exchange, the lung is critical for organismal survival. It is also subject to continual environmental insults inflicted by pathogens, particles, and toxins. Sometimes, these insults result in structural damage and the initiation of an innate immune response. Operating in parallel, the immune response aims to eliminate the threat, while the repair process ensures continual physiological function of the lung. The inflammatory response and repair processes are thus inextricably linked in time and space but are often studied in isolation. Here, we review the interplay of innate immune cells and nonimmune cells during lung insult and repair. We highlight how cellular cross talk can fine-tune the circuitry of the immune response, how innate immune cells can facilitate or antagonize proper organ repair, and the prolonged changes to lung immunity and physiology that can result from acute immune responses and repair processes.
The Integrated Pulmonary Immune Response to Pneumonia
Authors: Katrina E. Traber, Joseph P. Mizgerd
Journal: Annual Review of Immunology (2025)

Pneumonia is an acute respiratory infection of the lower respiratory tract. The effectiveness of the host immune response determines the severity of infection, or whether pneumonia occurs at all. The lungs house both innate and adaptive immune systems, which integrate their activities to provide host defense that eliminates microbes and prevents lower respiratory infection from becoming severe. Professional immune cells in the lung, like macrophages and lymphocytes, work with lung constituents, like epithelial cells and fibroblasts, to optimize antimicrobial defense. The dynamics of the immune response during infection and the immune components contributing to defense are influenced by prior experiences with respiratory pathogens, remodeling lung immunity in ways that improve responses against subsequent infections. This review covers how innate and adaptive immune activities coordinate inside the lung to provide integrated and effective immune resistance against respiratory pathogens.
PERK+ macrophages drive immunotherapy resistance in lymph node metastases of oral squamous cell carcinoma
Authors: Wei Zhang, Jin-Bang Li, Hai-Ming Liu, Kui-Ming Wang, Bo-Lin Xiao, Yi-Man Wang, Jia-Jie Liang, Jun Zeng, Lin-Zhou Zhang, Yang-Ying-Fan Feng, Qiu-Yun Fu, Xin-Xin Wang, Yu-Tong Liu, Xiao-Xia Cheng, Jing Li, Yu-Ying Zhang, Gao Zhang, Jia-Li Zhang, Zi-Li Yu, Zhe Shao, Xue-Peng Xiong, Jun Jia, Bing Liu, Gang Chen
Journal: Clinical Cancer Research (2025)

Neoadjuvant anti-PD-1 immunotherapy combined with chemotherapy has shown promising pathological responses in various cancers, including oral squamous cell carcinoma (OSCC). However, the pathological response of lymph node (LN) metastases remains poorly understood. This study aims to systematically evaluate the pathological response rates (pRRs) of LN metastases in OSCC patients and identify potential targets to improve therapeutic outcomes. We assessed the pRRs of LN metastases and matched primary tumors (PTs) in OSCC patients enrolled in a randomized, two-arm, phase II clinical trial (NCT04649476). Single-cell and spatial transcriptomics and multiplex immunohistochemistry were performed to analyze the tumor microenvironment and identify potential therapeutic targets in LN metastases. A neoadjuvant orthotopic OSCC mouse model was established to evaluate the therapeutic potential of these targets. We observed significant heterogeneity in pathological regression of LN metastases, with lower pRRs compared to PTs. pRRs in LN metastases were correlated with overall and disease-free survival in OSCC patients. We identified an abundance of macrophages in LN metastases exhibiting an unfolded protein response and activated PERK signaling. These macrophages contributed to an extracellular matrix-enriched microenvironment through interactions with fibroblasts, which hindered T cell-mediated cytotoxicity. Pharmacological inhibition of the PERK pathway significantly enhanced anti-PD-1 therapy in LN metastases and PTs in the mouse model. Our study confirms that the pathological response of LN metastases in OSCC patients undergoing neoadjuvant immunotherapy or immunochemotherapy is inferior to that of PTs. It suggests targeting the PERK pathway in macrophages could be a potential strategy to enhance treatment outcomes.
Fine particulate matter exposure and incident atopic dermatitis: A birth cohort study
Authors: Lih-Hwa Lin, Chung-Chin Lee, Meng-Min Hwang, Chau-Ren Jung, I-Hsiu Lai, Wei-Ting Chen, Bing-Fang Hwang
Journal: British Journal of Dermatology (2025)

Understudied the association between exposure to fine particulate matter (PM2.5) from conception to one year after birth and later development of atopic dermatitis (AD) has not been completely elucidated. To investigate the effects of PM2.5 exposure during pregnancy and infancy on AD and explore sensitive time windows to identify biological pathways of the effects of PM2.5 on AD. A birth cohort study comprising 564,869 term births born between 2004-2013 and followed up until 5 years after birth. A satellite-based model was used to calculate PM2.5 exposure for each child. A Cox proportional hazard model combined with a distributed lag non-linear model was performed to examine the associations of AD with PM2.5, as well as the dose-response relationship. The birth cohort comprised of 76,944 cases diagnosed with AD. Increased cumulative exposure to PM2.5 from 34 weeks of gestation until birth, as well as from 33 weeks after birth during infancy, was significantly associated with a higher incidence of AD. In the dose-response relationship, exposure to PM2.5 more than 65 μg/m3 might sharply increase the risk of AD. Both prenatal and postnatal exposures to PM2.5 were related to later development of AD. The susceptible time windows may be late gestation and early life after birth.
Effect of Brief Maternal Exposure to Bisphenol A on the Fetal Female Germline in a Mouse Model
Authors: Lisa A. Vrooman, Mary C. Gieske, Crystal Lawson, Joseph Cesare, Shuo Zhang, Marisa S. Bartolomei, Benjamin A. Garcia, Terry J. Hassold, Patricia A. Hunt
Journal: Environmental Health Perspectives (2025)

Environmental contamination by endocrine disrupting chemicals (EDCs) has created serious public health, ecological, and regulatory concerns. Prenatal exposures can affect a wide range of developing organ systems and are associated with adverse changes to behavior, metabolism, fertility, and disease risk in the adult. The most serious and puzzling observation for some EDC exposures is the transmission of effects to subsequent unexposed generations (transgenerational effects) in animal models. This requires the induction of epigenetic aberrations to the germline that are not subject to the normal processes of erasure and resetting in subsequent generations. Understanding when and how the germline is vulnerable to environmental contaminants is an essential first step in devising strategies to prevent and reverse their effects. Fetal mouse oocytes were collected after exposure of the dam to various concentrations of bisphenol A (BPA) or placebo. Meiotic effects were assessed by immunostaining to visualize the synaptonemal complex and recombination sites, as well as whole chromosome fluorescence in situ hybridization probes. Enriched oocyte pools were analyzed by mass spectrometry and RNA sequencing to determine differences in histone post-translational modifications and gene expression, respectively. We found germline effects across a wide range of exposure levels, the severity of which was positively associated with BPA concentration. We identified the onset of meiotic prophase as the vulnerable window of exposure and found surprising exposure-related differences in chromatin. Oocyte analysis by mass spectrometry and immunofluorescence suggested H4K20me2, a histone posttranslational modification involved in DNA damage repair, was particularly affected. Subsequent RNA-seq analysis revealed a relatively small number of differentially expressed genes, but in addition to genes involved in chromatin dynamics, several with important roles in DNA repair/recombination and centromere stability were affected. Together, our data from a mouse model suggest BPA exposure induced complex molecular differences in the germline that dysregulated chromatin and affected several critical and interrelated meiotic pathways. https://doi.org/10.1289/EHP15046.
Surrogate endpoints for overall survival in randomized clinical trials testing antibody-drug conjugates
Authors: Laura Pala, Federico Merlo, Isabella Sala, Eleonora Pagan, Chiara Oriecuia, Claudia Specchia, Chiara Catania, Emilia Cocorocchio, Daniele Laszlo, Giovanni Ceresoli, Marzia Locatelli, Tommaso De Pas, Alberto Zambelli, Javier Cortes, Giuseppe Giaccone, Kathleen N Moore, Aditya Bardia, Giuseppe Viale, Richard D Gelber, Vincenzo Bagnardi, Fabio Conforti
Journal: JNCI Journal of the National Cancer Institute (2025)

The surrogacy of overall response-rate (ORR) or progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing antibody-drugs conjugates (ADC) has never been investigated. RCTs testing ADCs in patients with advanced solid tumors and reporting data on OS and PFS and/or ORR were analyzed.The main objective was to assess the trial-level association between the surrogate endpoints (ORR or PFS) and the reference endpoint (OS), overall and in subgroups of trials defined by tumor type, number of previous lines of systemic treatments, and specific ADC features. Twenty-five RCTs, for a total of 26 treatment comparisons and 11,729 patients, were included in the analysis. In 21 comparisons the ADC was administered as monotherapy, and in 16 was tested in patients with breast cancer.The association between the hazard ratio for OS and relative risk of ORR was moderate: the R2 from a model adjusted by tumor type was 0.47 (95%CI,0.11-0.83).The association between the hazard ratios for OS and PFS was strong: the R2 from the adjusted model was 0.79 (95%CI,0.66-0.92).Cross-validation analyses showed similar results. Consistent results were obtained across all the subgroups analyzed, with the notable exception of the subgroup of trials testing ADCs for breast cancer, where the association between OS and ORR appeared strong (R2=0.77; 95%CI,0.51-0.90). In RCTs evaluating ADCs in advanced solid tumors, PFS serves as a robust surrogate endpoint for OS, offering greater reliability than ORR and adequately supporting accelerated approval of ADCs in future trials.
Structural inequities in the availability of prostate cancer clinical trial opportunities
Authors: Rishi Robert Sekar, Laura Zebib, Kristian Donald Stensland, Lindsey Allison Herrel
Journal: JNCI Journal of the National Cancer Institute (2025)

Prostate cancer is marked by vast disparities in clinical outcomes for minoritized and socioeconomically disadvantaged populations. We aimed to evaluate the geographic distribution of prostate cancer clinical trial opportunities relative to prostate cancer mortality and social determinants of health by performing an ecological analysis of linked county-level prostate cancer clinical trial data, epidemiologic data, and the Centers for Disease Control and Prevention Social Vulnerability Index. On analysis of 1,575 counties in the United States with available data, increasing SVI was associated with an increase in prostate cancer mortality (+17.88, 95% CI 14.16-21.61, p < .001), lower odds of having any trial (OR 0.14, 95% CI 0.09-0.23, p < .001), and fewer population-adjusted trials (IRR 0.27, 95% CI 0.19-0.40, P < .001). Identifying communities experiencing adverse social determinants of health for expansion of clinical trial opportunities and mitigation of barriers may be an impactful strategy towards improving equity in clinical trials and cancer care.
Patient research priorities in melanoma: a national qualitative interview study
Authors: Khaylen Mistry, Omsin Srimudkul, Mitesh Patel, John Ragan, Dimitrios Karponis, Zoe C Venables, Nick J Levell
Journal: British Journal of Dermatology (2025)

Outcomes for advanced melanomas have improved following the advent of immunotherapy and targeted therapy. This heralds a need for reconsideration of future research agendas. Patients can, and are keen to help identify and prioritise research topics to ensure future research benefits patients. No previous peer-reviewed research has reported patient research priorities for melanoma. To determine melanoma patients' prioritised research topics in England. Patients ≥18 years, diagnosed with melanoma within the past ten years were recruited across England by skin cancer charities. Pre-interview questionnaires obtained demographic, tumour and treatment information. Semi-structured interviews were conducted where patients were asked what they thought were important topics to research in melanoma. Using a grounded theory approach, transcripts were analysed in an iterative process to identify themes for patient research priorities. Twenty patients were individually interviewed from 8/9 English regions. Five key themes were identified. (1) Risk factors and prevention of melanoma. Patients voiced desire for research into modifiable risk factors and public campaigns to prevent melanoma. (2) Diagnostic delay and misdiagnosis of melanoma. Patients felt diagnostic delays could be reduced through research to support non-specialists and integrating technology such as teledermatology or artificial intelligence. (3) Indications, outcomes, side effects and interactions of treatments for melanoma. Novel treatments inspired patients to encourage future research into the indications, outcomes and side effects of therapeutic options. (4) Optimising follow-up for melanoma. With increased survivorship, research to support the delivery of a personalised approach to follow-up was valued. (5) Factors that influence survival from melanoma. Patients prioritised research to accurately predict recurrence and survival based on patient-specific factors. This is the first peer-reviewed study to report patient research priorities in melanoma. Many of the themes identified align with NICE research recommendations. Additionally, novel themes were identified which provides rationale to develop a James Lind Alliance Priority Setting Partnership for melanoma. If research addresses topics relevant to patients, decision-makers will be equipped to deliver services which meet patient needs.
Ipilimumab + nivolumab combination or nivolumab monotherapy as first-line treatment in patients with metastatic melanoma: conclusions from a real-world French national cohort
Authors: Charlée Nardin, Dewi Vernerey, François Aubin
Journal: British Journal of Dermatology (2025)

Journal Article Accepted manuscript Ipilimumab + nivolumab combination or nivolumab monotherapy as first-line treatment in patients with metastatic melanoma: conclusions from a real-world French national cohort Get access Charlée Nardin, Charlée Nardin Hôpital Jean Minjoz, Besançon, Bourgogne-Franche-Comté, France Corresponding author: Charlée Nardin, MD PhD, Email:[email protected] https://orcid.org/0000-0002-9902-5990 Search for other works by this author on: Oxford Academic Google Scholar Dewi Vernerey, Dewi Vernerey Methodology and Quality of Life Unit in Oncology, Besançon University Hospital Center, Besançon, Bourgogne-Franche-Comté, France Search for other works by this author on: Oxford Academic Google Scholar François Aubin François Aubin Methodology and Quality of Life Unit in Oncology, Besançon University Hospital Center, Besançon, Bourgogne-Franche-Comté, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljaf080, https://doi.org/10.1093/bjd/ljaf080 Published: 27 February 2025 Article history Received: 21 February 2025 Accepted: 24 February 2025 Published: 27 February 2025
Congenital melanocytic nevi initiated by <i>BRAF</i> fusion oncogene with firmness, pruritus, and desmoplastic stroma
Authors: Simon F Roy, Nnenna G Agim, Adnan Mir, Kasey L Couts, Travis Vandergriff, William A Robinson, Boris C Bastian, Ilona Frieden, Iwei Yeh
Journal: British Journal of Dermatology (2025)

Large and giant congenital melanocytic nevi present a risk for developing melanoma or neurocutaneous melanosis. Most are caused by NRAS or, less commonly, BRAF mutations. We present a series of patients with large to giant congenital melanocytic nevi with BRAF fusion genes as driver alterations and describe their unique clinical presentation. We retrospectively identified five patients with giant congenital melanocytic nevi harboring BRAF fusion genes, from three academic institutions. We analyzed tumor DNA using capture-based next-generation sequencing. Four of five patients with giant congenital melanocytic nevi harboring a BRAF fusion gene exhibited thousands of satellite nevi, many with significant pruritus, nodularity and firmness. One patient developed neurocutaneous melanosis. Histopathology showed marked stromal desmoplasia, akin to the changes observed in acquired melanocytic nevi with BRAF fusion genes. Notably, one case responded to the MEK inhibitor trametinib, demonstrating the potential therapeutic advantage of genetic characterization of these lesions. Congenital melanocytic nevi with BRAF fusion genes appear to have unique clinical features and may be associated with numerous satellite lesions. Marked desmoplasia is a histopathologic feature that can point towards an underlying BRAF fusion gene.
Pre- and post-diagnostic use of antihypertensive medications and stage I-III colorectal cancer survival: prospective cohort study
Authors: Yue Liu, Mingyang Song, Edward L Giovannucci, Elizabeth A Platz
Journal: JNCI Journal of the National Cancer Institute (2025)

Antihypertensive medications have been investigated in relation to colorectal cancer (CRC)-specific survival. To address limitations and important unanswered questions in the existing evidence, we investigated associations of pre- and post-diagnostic use of antihypertensive classes-beta-blockers, calcium channel blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, furosemide, and other antihypertensives-with CRC-specific mortality among 2,182 patients with stage I-III CRC in the Nurses' Health Study and Health Professionals Follow-up Study in a prospective cohort study with long-term follow-up, repeat assessments of antihypertensive use, and rigorous confounding control. Pre- and post-diagnostic use of each antihypertensive class studied was not clearly associated with stage I-III CRC survival compared with either non-users or with patients with high blood pressure who used any other antihypertensives. While we did not detect an association for overall use of specific antihypertensives, future investigations should investigate drug dose and interactions between antihypertensive medications and cancer therapies with CRC survival.
Re: Timing of depression in relation to risk of ovarian cancer
Authors: Steven Lehrer
Journal: JNCI Journal of the National Cancer Institute (2025)

Journal Article Accepted manuscript Re: Timing of depression in relation to risk of ovarian cancer Get access Steven Lehrer, MD Steven Lehrer, MD Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Corresponding author: Dr Steven Lehrer, Box 1236 Radiation Oncology, Mount Sinai Medical Center, 1 Gustave L. Levy Place, New York, NY 10029, USA. Email: [email protected]. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, djaf043, https://doi.org/10.1093/jnci/djaf043 Published: 25 February 2025 Article history Received: 07 January 2025 Accepted: 09 January 2025 Published: 25 February 2025