Oncoimmunology最新文献

{"title":"Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells.","authors":"Meng Li, Di Li, Hai-Yun Wang, Weixin Zhang, Zhenjian Zhuo, Huiqin Guo, Jiabin Liu, Yue Zhuo, Jue Tang, Jing He, Lei Miao","doi":"10.1080/2162402X.2025.2460281","DOIUrl":"10.1080/2162402X.2025.2460281","url":null,"abstract":"<p><p>The exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data in mediastinal NB tissues, we found that the content of long-chain acylcarnitine (LCAC) was increased and positively associated with leptin expression in advanced NB. Leptin over-expression forced naïve CD4+ T cells to differentiate into Treg cells instead of Th17 cells, which benefited from NB cell proliferation, migration, and drug resistance. Mechanically, leptin in NB cells blunted the activity of carnitine palmitoyltransferase 2 (CPT2), the key enzyme for LCAC catabolism, by inhibiting sirtuin 3-mediated CPT2 deacetylation, which depresses oxidative phosphorylation (OXPHOS) for energy supply and increases lactic acid (LA) production from glycolysis to modulate CD4+ T cell differentiation. These findings highlight that excess leptin contributes to lipid metabolism dysfunction in NB cells and subsequently misdirects CD4+ T cell differentiation in tumor micro-environment (TME), indicating that targeting leptin could be a therapeutic strategy for retarding NB progression.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2460281"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long-lasting expression of recombinant artLCMV following intraperitoneal administration exerts potent antitumor effects on tumor models of peritoneal carcinomatosis.","authors":"Celia Gomar, Aline Risson, Leire Arrizabalaga, Nuria Ardaiz, Virginia Belsue, Adrian Gil-Korilis, Sarah Ahmadi-Erber, Timo Schippers, Ignacio Melero, Klaus K Orlinger, Fernando Aranda, Henning Lauterbach, Pedro Berraondo","doi":"10.1080/2162402X.2025.2520266","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2520266","url":null,"abstract":"<p><p>Peritoneal carcinomatosis remains a challenging clinical condition with limited therapeutic options. In this study, we evaluated the efficacy of a recombinant artLCMV platform encoding tumor antigens and immune-stimulatory molecules in preclinical models. We analyzed the expression kinetics, biodistribution, and antitumor activity of artLCMV vectors encoding the reporter protein NanoLuc, tumor-associated antigens such as gp70 or folate receptor alpha (FRα), and immune-stimulatory molecules including IL12 or 4-1BBL. These vectors were tested in murine models of peritoneal carcinomatosis established by intraperitoneal inoculation of MC38 colon cancer cells or ID8-VEGF ovarian cancer cells. Intraperitoneal administration of artLCMV-NanoLuc resulted in sustained, high-level transgene expression in the peritoneal cavity for over 40 days. The antitumor efficacy of artLCMV.gp70 was significantly enhanced by IL12, eliciting a robust immune response in the MC38 model. In contrast, artLCMV.gp70 and artLCMV.FRα effectively reduced tumor burden and prolonged survival in ID8-VEGF mice, but coexpression of IL12 or 4-1BBL did not provide additional therapeutic benefit. These findings demonstrate that recombinant artLCMV vectors offer a promising therapeutic strategy for peritoneal carcinomatosis, delivering long-lasting transgene expression and potent antitumor effects. The addition of immunostimulatory molecules such as IL12 may enhance efficacy in certain tumor models, though its effects appear to be context-dependent.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2520266"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and immunological features associated with long-term benefits in metastatic NSCLC patients undergoing immune checkpoint blockade.","authors":"Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, Nil Navarro-Gorro, Adrià Rossell, Xavier Villanueva, Mario Giner, Ignacio Sanchéz, Miguel Galindo, Raúl Del Rey-Vergara, Albert Iñañez, Beatriz Sanchéz-Espiridion, Wei Lu, Ariadna Acedo-Terrades, Pau Berenguer-Molins, Albert Sánchez-Font, Roberto Chalela, Victor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James White, Jennifer B Jackson, Laura Moliner, Sergi Clavé, Beatriz Bellosillo, Ana Rovira, Ignacio Wistuba, Luisa M Solis Soto, Júlia Perera-Bel, Edurne Arriola","doi":"10.1080/2162402X.2025.2469377","DOIUrl":"10.1080/2162402X.2025.2469377","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.</p><p><strong>Methods: </strong>A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. Plasma ctDNA next-generation sequencing panel (NGS) and serum proteomics were performed. GeoMx DSP on baseline tumor tissue was performed in a subset of patients.</p><p><strong>Results: </strong>Our analysis revealed specific characteristics of LTR compared with STR, namely higher PD-L1 in tumor cells (<i>p</i> = 0.005) and higher incidence of irAEs (<i>p</i> = 0.001). Genomic features associated with lack of benefit from ICB included co-occurring mutations in KRAS/STK11 and TP53/KMT2D (<i>p</i> < 0.05). At a baseline, LTR patients exhibited higher serum levels of proteins related with apoptosis (CASP8, PRKRA), chemotaxis, immune proteasome, processing of MHC class I (S100A4, PSMD9, RNF41) and immune homeostasis (HAVCR1, ARG1) (<i>p</i> < 0.05). Protein spatial profiling of tumor samples showed higher levels of proteins linked with the presence of immune cells (CD45), T cells (CD8), antigen presentation (HLA-DR) and immune regulation proteins (PD-L1, IDO1) within the tumor and tumor stroma component (<i>p</i> < 0.05) in LTR patients. Serum longitudinal analysis identified a set of proteins that presented distinct dynamics in LTR compared to STR, making them interesting candidates to evaluate as early predictors of treatment efficacy.</p><p><strong>Conclusions: </strong>Our multimodal analysis of patients with metastatic NSCLC treated with ICB identified clinicopathological and immunological features associated with long-term benefits. The presence of preexisting antitumor immunity emerged as a strong predictor of long-term benefits, providing insights for potential biomarkers and therapeutic strategies for enhancing ICB outcomes in metastatic NSCLC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2469377"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.","authors":"Kengo Tanigawa, William L Redmond","doi":"10.1080/2162402X.2025.2452654","DOIUrl":"10.1080/2162402X.2025.2452654","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) has significantly improved the survival for many patients with advanced malignancy. However, fewer than 50% of patients benefit from ICB, highlighting the need for more effective immunotherapy options. High-dose interleukin-2 (HD IL-2) immunotherapy, which is approved for patients with metastatic melanoma and renal cell carcinoma, stimulates CD8⁺ T cells and NK cells and can generate durable responses in a subset of patients. Moreover, HD IL-2 may have potential efficacy in patients whose disease has progressed following ICB and plays a vital role in expanding tumor-infiltrating lymphocyte (TIL) in TIL therapy. Despite its potential, the use of HD IL-2 is limited by severe toxicities such as hypotension and vascular leak syndrome. Additionally, only a few patients achieve a good outcome after HD IL-2 therapy. To address these challenges, numerous next-generation IL-2 receptor (IL-2 R) agonists have been developed to exhibit treatment effects while minimizing adverse events. This review will explore IL-2 biology, the clinical application of HD IL-2 therapy, and the development of novel IL-2 R agonists for cancer immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2452654"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-related hepatitis and hypophysitis are associated with superior survival in melanoma patients treated with combined ipilimumab and nivolumab.","authors":"Hifaa Al Remawi, Maria Lindén, Zhiyuan Zhao, Ankur Pandita, Anna Rudin, Lars Ny, Sara Bjursten, Max Levin","doi":"10.1080/2162402X.2025.2543510","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2543510","url":null,"abstract":"<p><p>Combination CTLA-4 (ipilimumab) and PD-1 (nivolumab) checkpoint inhibition (dual-ICI) improves survival in patients with advanced melanoma. However, many patients also experience immune-related adverse events (irAE) that require systemic treatment with corticosteroids. Corticosteroids dampen the anti-tumoral response and may impair survival. Here, we investigated the association between irAE and overall survival as well as exposure to corticosteroids and second line immunosuppressants in dual ICI-treated patients with advanced melanoma (<i>n</i> = 205). Patients with irAE (<i>n</i> = 113) had superior OS compared to patients with no irAE (<i>n</i> = 92). The survival benefit persisted after adjusting for immortal time bias. Regarding specific irAE, patients with colitis, hepatitis, rheumatic irAE, hypophysitis, and skin-related irAE had improved OS after adjusting for negative baseline factors. A survival benefit persisted for hypophysitis (<i>p</i> = 0.03) and hepatitis (<i>p</i> = 0.04) after adjusting for immortal time bias, whereas rheumatic (<i>p</i> = 0.05) and skin-related irAE (<i>p</i> = 0.06) where borderline significant. Hepatitis and colitis required higher doses of corticosteroids for longer times and more often second-line immunosuppression compared to other irAE. In conclusion, irAE are associated with superior OS in patients with advanced melanoma treated with dual ICI. Hepatitis and hypophysitis were most strongly associated with better survival outcomes. Studies investigating the mechanisms underlying hepatitis and hypophysitis may identify important response mechanisms.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2543510"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphodepletion, tumor-infiltrating lymphocytes, and high versus low dose IL-2 followed by pembrolizumab in patients with metastatic melanoma.","authors":"Merve Hasanov, Simin Kiany, Marie-Andrée Forget, Roland Bassett, Michael A Davies, Adi Diab, Jeffrey E Gershenwald, Isabella C Glitza, Jeffrey E Lee, Anthony Lucci, Jennifer L McQuade, Sapna P Patel, Merrick I Ross, Hussein A Tawbi, Jennifer A Wargo, Michael K Wong, Chantale Bernatchez, Patrick Hwu, Cara Haymaker, Rodabe N Amaria","doi":"10.1080/2162402X.2025.2546402","DOIUrl":"10.1080/2162402X.2025.2546402","url":null,"abstract":"<p><p>This study evaluated the efficacy and safety of unengineered tumor-infiltrating lymphocytes (TILs) combined with pembrolizumab and either high (HD, Arm-1) or low (LD, Arm-2) doses of IL-2 in patients with metastatic melanoma (MM). Patients were lymphodepleted with cyclophosphamide and fludarabine, followed by TIL infusion and IL-2 (Arm-1: 720,000 IU/kg IV q 8 hrs up to 15 doses; Arm-2: 2 million IU SC for 14 days). Patients received pembrolizumab 200 mg IV starting 21 days post-TIL infusion, and every 3 weeks for up to 2 years. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Blood samples were collected for longitudinal flow cytometry and cytokine analysis. In Arm-1 (<i>n</i> = 7), one patient had a partial response (PR) for 10 months, two had stable disease (SD), three had progressive disease (PD), and one was not evaluable (NE). In Arm-2 (<i>n</i> = 7), one patient had an ongoing PR for over 76 months, one had SD, and five had PD. The toxicity profiles were comparable; however, patients in Arm-2 had lower grade 3 febrile neutropenia (57% vs. 71%) and shorter hospitalization (median 16 days vs. 18 days). No correlation was observed between TIL phenotype and clinical response, although PR patients received high numbers of TIL with a high CD8⁺/CD4⁺ T cell ratio. IL-2 dose did not affect the frequency, phenotype, or proliferation of circulating T cell subsets, and anti-PD-1 did not boost T-cell proliferation. No significant differences were observed between IL-2 doses, suggesting low-dose IL-2 as an alternative to high-dose IL-2 after TIL administration.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2546402"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamate promotes CCL2 expression to recruit tumor-associated macrophages by restraining EZH2-mediated histone methylation in hepatocellular carcinoma.","authors":"Jing Chen, Hong-Wei Sun, Run-Zheng Wang, Yun-Fei Zhang, Wen-Jiao Li, Yong-Kui Wang, Hao Wang, Miao-Miao Jia, Qing-Xia Xu, Hao Zhuang, Ning Xue","doi":"10.1080/2162402X.2025.2497172","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2497172","url":null,"abstract":"<p><p>Glutamate is well-known as metabolite for maintaining the energy and redox homeostasis in cancer, moreover it is also the primary excitatory neurotransmitter in the central nervous system. However, whether glutamatergic signaling can regulate hepatocellular carcinoma (HCC) progression and the specific regulatory mechanisms are unknown. In the present study, we found that glutamate and its receptor NMDAR2B were significantly elevated in HCC patients, which predicts poor prognosis. Glutamate could upregulate CCL2 expression on hepatoma cells and further enhance the capability of tumor cells to recruit tumor-associated macrophages (TAMs). Mechanistically, glutamate could facilitate CCL2 expression through NMDAR pathway by decreasing the expression of EZH2, which regulates the H3K27me3 levels on the CCL2 promoter, rather than affecting DNA methylation. Moreover, inhibiting glutamate pathway with MK801 could significantly delay tumor growth, with reduced TAMs in implanted Hepa1-6 mouse HCC models. Our work suggested that glutamate could induce CCL2 expression to promote TAM infiltration by negatively regulating EZH2 levels in hepatoma cells, which might serve as a potential prognostic marker and a therapeutic target for HCC patients.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2497172"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12026252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the atypical chemokine receptor 2 (<i>Ackr2</i>) improves the benefit of anti-PD-1 immunotherapy in melanoma mouse model.","authors":"Muhammad Zaeem Noman, Martyna Szpakowska, Malina Xiao, Ruize Gao, Kris Van Moer, Akinchan Kumar, Markus Ollert, Guy Berchem, Andy Chevigné, Bassam Janji","doi":"10.1080/2162402X.2025.2494426","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2494426","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) therapies, such as anti-PD-1, have transformed cancer treatment, but many patients do not respond due to a non-inflammatory tumor microenvironment (TME). Here, we investigated the impact of targeting Atypical Chemokine Receptor 2 (<i>ACKR2</i>), which scavenges key chemokines involved in immune cell recruitment, on the improvement of anti-PD-1-based therapy. In a melanoma mouse model, we demonstrated that <i>Ackr2</i> inhibition increases the release of proinflammatory chemokines CCL5 and CXCL10 and enhances the infiltration of NK cells, activated CD8+ and CD4+ effector T cells while reducing regulatory T cells (Tregs) in the TME. Targeting <i>Ackr2</i> led to tumor growth inhibition, improved survival, and enhanced response to anti-PD-1 therapy. In BRAF- and NRAS-mutant melanoma patients, low <i>ACKR2</i> expression or high CCL5/CXCL10 levels correlated with improved survival and higher CD8+ T cell markers. Targeting <i>ACKR2</i> represents a promising approach for developing combination therapies, particularly for 'cold' ICB resistant tumors.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2494426"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gasdermin E links tumor cell-intrinsic nucleic acid signaling to proinflammatory cell death for successful checkpoint inhibitor cancer immunotherapy.","authors":"Stefan Enssle, Anna Sax, Peter May, Nadia El Khawanky, Nardine Soliman, Markus Perl, Julius C Enssle, Karsten Krey, Jürgen Ruland, Andreas Pichlmair, Florian Bassermann, Hendrik Poeck, Simon Heidegger","doi":"10.1080/2162402X.2025.2504244","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2504244","url":null,"abstract":"<p><p>Durable clinical responses to immune checkpoint inhibitors (ICI) are limited to a minority of patients, and molecular pathways that modulate their efficacy remain incompletely defined. We have recently shown that activation of the innate RNA-sensing receptor RIG-I and associated apoptotic tumor cell death can facilitate tumor immunosurveillance and -therapy, but the mechanism that drives its immunogenicity remained unclear. We here show that intratumoral activity of the pore-forming protein gasdermin E (GSDME) links active RIG-I signaling and apoptotic cell death in tumor cells to inflammatory pyroptosis. Activation of tumor-intrinsic RIG‑I triggered cleavage of GSDME, pore formation, loss of cell membrane integrity and leakage of cytosolic components from dying tumor cells. Tumor antigen cross-presentation by dendritic cells and subsequent expansion of cytotoxic T cells strongly relied on tumor-intrinsic GSDME activity. In preclinical murine cancer models, defective GSDME signaling rendered tumors resistant to ICI therapy. Epigenetic reprogramming with upregulation of <i>Gdsme</i> enhanced the susceptibility of tumor cells to inflammatory cell death and immunotherapy. In humans, transcriptome analysis of melanoma samples showed strong correlation between genetic activity of the RIG-I and pyroptosis pathways. In melanoma patients, high transcriptional activity of a pyroptosis gene set was associated with prolonged survival and beneficial response to ICI therapy. In summary, our data show that GSDME links RIG-I and apoptotic signaling to inflammatory cell death, thereby driving its immunogenicity and responsiveness to ICI. A deeper understanding of these pathways may allow for the development of novel combined modality approaches to improve ICI treatment responses in cancer patients.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2504244"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-disease integration of single-cell RNA sequencing data from lung myeloid cells reveals TAM signature in <i>in vitro</i> model.","authors":"Catarina Pinto, Jakub Widawski, Sophie Zahalka, Barbara Thaler, Linda C Schuster, Samuel W Lukowski, Fidel Ramírez, Iñigo Tirapu","doi":"10.1080/2162402X.2025.2502278","DOIUrl":"10.1080/2162402X.2025.2502278","url":null,"abstract":"<p><p>Advancements in single-cell RNA sequencing (scRNA-seq) have revealed the phenotypic and functional diversity of tumor-associated macrophages (TAMs), identifying specific populations that directly impact the antitumor response. However, despite the recognition of TAMs as promising therapeutic targets for cancer treatment, research is hindered by the lack of validated human preclinical models. Here, we applied scRNA-seq to a 3D human cell-based model comprising tumor cell line-derived spheroids, cancer-associated fibroblasts and primary monocytes, a setup widely used in immuno-oncology research. Integration of our <i>in vitro</i> data with publicly available patient-derived datasets showed that the macrophages in this model share phenotypic characteristics with the pro-angiogenic and pro-fibrotic SPP1⁺ TAM population recently found across multiple cancer types and inflammatory lung diseases. This population was linked to aspects of disease progression and associated with poor prognosis in several tumor indications, highlighting the need for relevant models enabling its study as an immunotherapy target. Our research validates the use of a 3D human cell-based culture as a more in vivo-relevant model and enables the preclinical testing of novel macrophage-targeting drugs in a human disease-relevant setup.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2502278"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}