Oncoimmunology最新文献

{"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}

{"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":"Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer.","authors":"Carmen G Cañizo, Félix Guerrero-Ramos, Mercedes Perez Escavy, Iris Lodewijk, Cristian Suárez-Cabrera, Lucía Morales, Sandra P Nunes, Ester Munera-Maravilla, Carolina Rubio, Rebeca Sánchez, Marta Rodriguez-Izquierdo, Jaime Martínez de Villarreal, Francisco X Real, Daniel Castellano, Cristina Martín-Arriscado, David Lora Pablos, Alfredo Rodríguez Antolín, Marta Dueñas, Jesús M Paramio, Victor G Martínez","doi":"10.1080/2162402X.2024.2438291","DOIUrl":"10.1080/2162402X.2024.2438291","url":null,"abstract":"<p><p>High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest. Compared to non-tumoral tissue, NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution, such as increased macrophage infiltration. Heterogeneous PD-L1 expression was observed across subsets, with macrophages showing the highest expression levels, but cancer cells as the primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are specifically enriched in high-grade NMIBC tumors. The topological distribution of these two cell types changed as NMIBC progresses, as shown by immunofluorescence. Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2438291"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856324","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":"Plasma protein dynamics during ipilimumab treatment in metastatic melanoma: associations with tumor response, adverse events and survival.","authors":"Ragnhild Reehorst Lereim, Claire Dunn, Elin Aamdal, Sudhir Kumar Chauhan, Oddbjørn Straume, Tormod Kyrre Guren, Jon Amund Kyte","doi":"10.1080/2162402X.2024.2440967","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2440967","url":null,"abstract":"<p><p>The immune checkpoint inhibitor ipilimumab provides long term survival in some metastatic melanoma patients, but the majority has no benefit, and may experience serious side effects. Here, we investigated the dynamics of plasma cytokine concentrations and their potential utility for predicting treatment response, adverse events and overall survival (OS) in patients with metastatic melanoma undergoing ipilimumab monotherapy. A cohort of 148 patients was examined, with plasma samples collected prior to treatment initiation and at the end of the first and second treatment cycles. Concentrations of 48 plasma proteins were measured using a multiplex immunoassay. The results revealed a general increase in cytokine levels following the first ipilimumab dose, consistent with immune activation. Patients not responding to treatment exhibited significantly elevated baseline levels of G-CSF, IL-2RA, MIP-1a, and SCF, compared to tumor responders (<i>p</i> < 0.05). Furthermore, high levels of IL-2RA, IFNγ, PDGF-bb and MIG were linked to inferior OS, while high concentrations of MIF and RANTES were associated with improved OS (<i>p</i> < 0.05). A multivariate model containing CRP, LDH, ECOG, IL-2RA and PDGF-bb identified a subgroup of patients with poor OS. Patients who experienced severe immune-related adverse events within three months of treatment initiation had higher baseline concentrations of several cytokines, indicating a potential association between preexisting inflammation and adverse events. These findings indicate that the first dose of ipilimumab induces a systemic response with increased levels of circulating cytokines and suggest candidate biomarkers for clinical response, immune-mediated toxicity and survival. Further studies in independent patient cohorts are required to confirm the findings.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2440967"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866014","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":"TNFR2/CCR8 bispecific antibody enhances antitumor activity through depleting Ti-Tregs and boosting effector CD8⁺ T cell function.","authors":"Ran Wang, Jiefang Xu, Shipeng Cheng, Zhiyang Ling, Wangmo Sonam, Jichao Yang, Fuquan Jin, Jing Wen, Xiao Lu, Liyan Ma, Yaguang Zhang, Xiaoyu Sun, Chunyan Yi, Bing Sun","doi":"10.1080/2162402X.2025.2497171","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2497171","url":null,"abstract":"<p><p>Modulation or depletion of tumor-infiltrating Tregs (Ti-Tregs) is a promising strategy in the field of antitumor immunotherapy. However, this approach poses challenges due to the diversity within the Treg population and the lack of precision in targeting Ti-Tregs. To selectively and efficiently eliminate Ti-Tregs while sparing other immune cells, we developed a bispecific antibody, FT10-Fab, targeting TNFR2 and CCR8, which are highly expressed on Ti-Tregs. Our results showed that FT10-Fab outperformed the monotherapies in several tumor models by significantly reducing the proportion of Ti-Tregs while increasing the proportion of CD8⁺ T cells. FT10-Fab was able to target and eliminate Ti-Tregs expressing TNFR2 or CCR8 (TNFR2⁺or CCR8⁺ Tregs), particularly TNFR2⁺ CCR8⁺ Tregs, which are the most important proliferative and protumorigenic Tregs. In addition, FT10-Fab relies on CD8⁺ T cells for its antitumor function and induces robust immune memory. Furthermore, the combination of FT10-Fab with PD-1 blockade showed synergistic therapeutic efficacy against tumors by significantly suppressing Tregs and enhancing effector CD8⁺ T cell function. Taken together, our findings suggest that precision depletion of Ti-Tregs via the bispecific TNFR2/CCR8 antibody is a potential therapeutic for cancer immunotherapy, while combination with anti-PD1 amplifies the antitumor effect.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2497171"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988762","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":"Patient-specific HLA-I subtypes predict response to immune checkpoint blockade.","authors":"Kyrillus S Shohdy, Jack Atherton, Jessica Longland, Jennifer Alison, Manon Pillai, Fiona Thistlethwaite","doi":"10.1080/2162402X.2025.2462386","DOIUrl":"10.1080/2162402X.2025.2462386","url":null,"abstract":"<p><p>Specific shared HLA-I alleles were linked to the response to immune checkpoint blockade (ICB). We aimed to identify the HLA-A subtypes associated with maximum benefit from ICB. We compiled a clinical dataset of patients who underwent a CLIA-approved germline HLA status testing as part of various advanced immune and cell therapy trials undertaken at the Christie NHS Foundation Trust. A total of 285 patients were eligible for final analysis. We identified 15 HLA-A subtypes, the most common alleles being HLA-A02, HLA-A01, and HLA-A03. A02:01 showed a tumor lineage-specific distribution. One hundred and forty patients received ICB and had evaluable response status. Patients with A01 were associated with better clinical outcomes. No significant associations were observed between HLA-A subtypes and the incidence of immune-related adverse effects. HLA genotyping should be incorporated early in the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2462386"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469640","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":"Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer.","authors":"Esen Yonca Bassoy, Remya Raja, Thomas E Rubino, Fabian Coscia, Krista Goergen, Paul Magtibay, Kristina Butler, Alessandra Schmitt, Ann L Oberg, Marion Curtis","doi":"10.1080/2162402X.2025.2460276","DOIUrl":"10.1080/2162402X.2025.2460276","url":null,"abstract":"<p><p>Most high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic groups. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens with low expression in normal tissues and upregulated expression in OC. Using tissue microarrays, we assessed the protein expression of TTLL8 and POTEE and their association with patient outcomes in a large cohort of OC patients. TTLL8 was found to be expressed in 56.7% of OC and was associated with a worse overall prognosis. POTEE was expressed in 97.2% of OC patients and had no significant association with survival. In patient TILs, increases in cytokine production and tetramer-positive populations identified antigen-specific CD8 T cell responses, which were dependent on antigen presentation by HLA class I. Antigen-specific T cells triggered cancer cell killing of antigen-pulsed OC cells. These findings suggest that TTLL8, POTEE, and PKMYT1 are potential targets for the development of antigen-targeted immunotherapy in OC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2460276"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075951","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":"Humanized mouse models of <i>KRAS</i>-mutated colorectal and pancreatic cancers with HLA-class-I match for pre-clinical evaluation of cancer immunotherapies.","authors":"Maria E Davola, Olga Cormier, Madeleine Lepard, Jamie McNicol, Susan Collins, Joanne A Hammill, Christopher Silvestri, Jonathan L Bramson, Amy Gillgrass, Karen L Mossman","doi":"10.1080/2162402X.2025.2473163","DOIUrl":"10.1080/2162402X.2025.2473163","url":null,"abstract":"<p><p>Cancer immunotherapy promises to treat challenging cancers including <i>KRAS</i>-mutated colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). However, pre-clinical animal models that better mimic patient tumor and immune system interactions are required. While humanized mice are promising vehicles for pre-clinical immunotherapy testing, currently used cancer models retain limitations, such as lack of a human thymus for human leukocyte antigen (HLA)-based education of human T cells. As cytotoxic T lymphocyte (CTL) activity underlies many immunotherapies, we developed more clinically relevant <i>KRAS</i>-mutated CRC and PDAC humanized cancer models using transgenic NRG-A2 mice expressing HLA-A2.1 to enable HLA-class-I match between mouse tissues (including the thymus), the humanized immune system and human tumors. Using these novel humanized cancer models and a CTL-mediated combination (immuno)therapy with clinical potential, we were able to recapitulate the complexity and therapy-induced changes reported in patient biopsies, demonstrating the use of these HLA-matched models for pre-clinical validation of novel immunotherapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2473163"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525001","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":"Correction.","authors":"","doi":"10.1080/2162402X.2025.2517490","DOIUrl":"10.1080/2162402X.2025.2517490","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2517490"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334142","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":"Mutant p53-specific CD8TCR-therapy combined with a CD4TCR prevents relapse of cancer and outgrowth of micrometastases.","authors":"Vasiliki Anastasopoulou, Hans Schreiber, Ching-En Lee, Kazuma Kiyotani, Leo Hansmann, Yusuke Nakamura, Matthias Leisegang, Steven P Wolf","doi":"10.1080/2162402X.2025.2514041","DOIUrl":"10.1080/2162402X.2025.2514041","url":null,"abstract":"<p><p>Relapse remains challenging in the treatment of metastatic cancers. More than 50% of human cancers harbor mutant p53 (mp53) as a cancer-specific target. We present the spontaneously metastasizing tumor model Ag104A to advance mp53-specific T cell receptor engineered T cell therapy (TCR-therapy). We identified in Ag104A an autochthonous p53^D256E mutation as neoantigen recognized by a TCR isolated from CD8⁺ T cells (CD8TCR). Cloning of the Ag104A cancer revealed mp53 expression in >99% of cancer cells. Targeting mp53 by CD8TCR-therapy was initially therapeutic, but tumors escaped as cancer cells with reduced or lack of antigen expression. Therefore, we determined whether escape could be prevented by combining the mp53-specific CD8TCR with a CD4⁺ T cell-derived TCR (CD4TCR) recognizing a mutant antigen presented on the stroma of the cancer. No relapse occurred when the mp53-specific CD8TCR was combined with the stroma-recognizing CD4TCR. The combination therapy also prevented the development of macrometastases from cancer cells that had already spread to the lung at the time of TCR-therapy. Macrometastases were only observed after monotherapy. Thus, in a spontaneously metastatic model, tumor relapse and development of macrometastases can be prevented by combining a CD8TCR targeting an autochthonous p53-mutation with a mutation-specific CD4TCR recognizing tumor stroma.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2514041"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295083","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}