Oncoimmunology最新文献

{"title":"CD4 ^<b>+</b> cell depletion accelerates dendritic cell migration and enhances resident dendritic cell proliferation in tumor-draining lymph nodes.","authors":"Taiki Moriya, Mayuko Hashimoto, Mizuki Ueda, Tatsuya Aoyagi, Ayako Kawaguchi, Kentaro Takahashi, Kobayashi Tsukasa, Kazuki Doi, Hiroaki Hemmi, Tsuneyasu Kaisho, Satoshi Ueha, Koji Matsushima, Yutaka Kusumoto, Tatyana Chtanova, Michio Tomura","doi":"10.1080/2162402X.2026.2682054","DOIUrl":"10.1080/2162402X.2026.2682054","url":null,"abstract":"<p><p>Depletion of CD4⁺ cells during an anti-tumor immune response promotes tumor regression and accelerates proliferation of tumor-antigen-specific CD8⁺ T cells in draining lymph nodes (dLNs). However, the effect of the depletion on inter-organ kinetics of antigen presentation and qualitative changes in dendritic cells (DCs) are not yet understood. Here, we established a novel approach for simultaneous detection of cellular movement and cell cycle phase <i>in vivo</i> by KikGR/Fucci mice and used it to examine migratory and LN resident DC (LNDC) dynamics after CD4⁺ cell depletion. We found that CD4⁺ cell depletion enhanced migration of CD11c⁺ MHC class II^high migratory DCs from tumor to dLNs and induced activation-associated phenotypic changes, such as increased MHC class II expression. Despite reduced overall cellularity in tumor dLNs, LNDC numbers were relatively maintained. Within the LNDC compartment, CD4 depletion increased the relative abundance of a CD8α⁺CD11b⁺ subset and promoted influx and cell-cycle activity among newly recruited LNDCs. Publicly available single-cell RNA sequencing data further delineated ligand-receptor expression relationships, including <i>Flt3l-Flt3</i> and <i>Csf2-Csf2ra/Csf2rb</i> axes, within tumor dLNs. These findings reveal remodeling of DC migration, activation, and LNDC turnover within tumor dLNs in the context of CD4⁺ cell depletion, which enhanced anti-tumor immunity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2682054"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148220279","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":"Cancer associated fibroblast-T cell crosstalk promotes purinergic synthesis in non-small cell lung cancer (NSCLC).","authors":"Lilian Koppensteiner, Charles Lochenie, Richard A O'Connor, Layla Mathieson, Liam Neilson, Ahsan R Akram","doi":"10.1080/2162402X.2026.2709221","DOIUrl":"10.1080/2162402X.2026.2709221","url":null,"abstract":"<p><p>The most abundant stromal cells of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs), inhibit the cytotoxic T cell response in solid tumors. CD39 and CD73 together deplete extracellular ATP in the TME to produce adenosine, which can promote tumor immune evasion. We aimed to investigate the role of CAF-T-cell crosstalk in the adenosine pathway in NSCLC. CD4⁺ and CD8⁺ T cells were flow sorted from <i>in vitro</i> culture with or without CAFs, and RNA-Seq was performed using the nCounter platform (NanoString). The expression of cell surface markers involved in adenosine production was assessed using flow cytometry in CAFs and peripheral T cells from healthy donors or early NSCLC patients following <i>in vitro</i> co-culture. Purinergic synthesis of AMP and adenosine was measured by HPLC. TCGA data was used to investigate the translational relevance of adenosine signaling in NSCLC, and NanoString Geomx was performed to investigate differences in the transcriptomics of tumor stromas with a high versus low adenosine signature. CD4⁺ and CD8⁺ T cells isolated from <i>in vitro</i> co-culture with CAFs show upregulated expression of CD39 and CD73, which results in functionally relevant production of AMP and adenosine. TCGA data illustrates that adenosine signaling is predictive of poor outcome in lung squamous cell carcinoma. Spatial transcriptomics (GeoMx) of the tumor stroma of early untreated NSCLC patients shows a downregulation of immune-related genes in lung squamous-cell carcinoma. CAF T cell crosstalk promotes the expression of CD39 and CD73 on CAFs and T cells, resulting in an increased synthesis of AMP and adenosine <i>in vitro</i>.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2709221"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622293","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":"Umbilical cord blood natural killer cells improve anti-GD2 antibody efficacy in neuroblastoma: from mouse to human.","authors":"Mengjia Song, Yingxia Lan, Xiya Tan, Linnan Wu, Jia Zhu, Suying Lu, Feifei Sun, Min Gao, Junting Huang, Yi Que, Yu Zhang, Xiaona Fang, Mengzhen Li, Yumiao Mai, Juan Wang, Tong Xiang, Yizhuo Zhang","doi":"10.1080/2162402X.2026.2679315","DOIUrl":"10.1080/2162402X.2026.2679315","url":null,"abstract":"<p><p>Despite advances in anti-disialoganglioside (GD2) immunotherapy, high-risk neuroblastoma (NB) remains a clinical challenge. Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity is a potent mechanism of action of anti-GD2 antibody. However, dose-intensive chemotherapy causes NK cell depletion. Here, a positive association between intratumoral NK cell infiltration and anti-GD2 efficacy was first observed in clinical samples. We then established the unique advantages of <i>ex vivo</i> expanded and activated umbilical cord blood (UCB)-derived NK cells in terms of cytotoxicity, persistence, exhaustion resistance, and safety from preclinical models to clinical cases compared with patient-derived PB NK cells. Anti-GD2 antibody further enhanced the superiority of UCB NK cells in terms of their functional status, persistence, and capacity to remodel an immune-activated tumor microenvironment. Combined treatment with UCB NK cells and an anti-GD2 led to synergistic effects <i>in vitro</i> and in mice and achieved complete and partial responses in two patients with relapsed/refractory NB, with no additive toxicity. Mechanistically, the anti-GD2 antibody induced a \"high activating-low inhibitory\" phenotype in UCB NK cells, and donor UCB NK cells showed dynamically lower levels of immune checkpoints but higher levels of memory-like markers than those of recipient NK cells when combined with anti-GD2 therapy. Collectively, this study is the first translational investigation of UCB NK cells combined with anti-GD2 therapy in NB, bridging preclinical mechanistic insights into an early clinical proof-of-concept. A phase I study of UCB NK cell infusion combined with anti-GD2 therapy in children with high-risk, relapsed/refractory NB is ongoing at our center (NCT06631391).</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2679315"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057717","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":"Histidine-improved cancer immunosurveillance.","authors":"Marine Fidelle, Ella Reich, Laurence Zitvogel, Guido Kroemer","doi":"10.1080/2162402X.2026.2713805","DOIUrl":"10.1080/2162402X.2026.2713805","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2713805"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760134","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":"Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.","authors":"Bianca M Balzasch, Andreas von Kries, Saskia Hüll, Indra A Shaltiel, Kim E Boonekamp, Volker Ast, Elke Burgermeister, Johannes Betge, Matthias Ebert, Michael Boutros, Laura Helming, Viktor Umansky, Adelheid Cerwenka","doi":"10.1080/2162402X.2026.2633012","DOIUrl":"10.1080/2162402X.2026.2633012","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) and monocytes that accumulate in colorectal cancer (CRC) play a crucial role in shaping the tumor microenvironment (TME) and anti-tumor immune responses. Although TAMs have been linked to both pro- and anti-tumor functions, our understanding of the cues instructing their heterogeneous phenotypes and function in cancer patients remains limited. Here, we established co-cultures comprising primary human monocytes and patient-derived organoids (PDOs) from patients with microsatellite-stable CRC to emulate myeloid/tumor cell interactions <i>in vitro</i>. Upon encountering PDOs, monocytes acquire phenotypic changes that are distinct from those induced by typical polarization protocols. Single-cell RNA sequencing revealed that PDO-exposed monocytes transcriptionally resembled IL1B-programmed monocytes previously identified in the tumor tissues of CRC patients. This phenotype emerged independently of tumor mutational profiles or consensus molecular subtypes. Mechanistically, soluble PDO-derived mediators induced the production of CXCL2, CXCL5 and CXCL7 chemokines, whereas the phagocytic uptake of tumor debris impaired the MHC class II-mediated antigen presentation capabilities of monocytes in co-culture. In addition, our <i>in vitro</i> system allowed functional assessment of PDO-exposed monocytes demonstrating a compromised capacity to mount an inflammatory response upon TLR stimulation. Together, PDO-monocyte co-cultures offer a platform to dissect the interplay between cancer cells and monocytes, and advance our understanding of myeloid plasticity and function in cancer patients.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2633012"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776719","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":"Virus nanoparticle intratumoral vaccines for HER2⁺ malignancies.","authors":"Miguel A Moreno-Gonzalez, Jessica Fernanda Affonso de Oliveira, Manuel L Penichet, Nicole F Steinmetz","doi":"10.1080/2162402X.2025.2583553","DOIUrl":"10.1080/2162402X.2025.2583553","url":null,"abstract":"<p><p>Our laboratory specializes in the intratumoral (i.t.) delivery of virus nanoparticles (VNPs) that activate immune cells and modulate the tumor microenvironment (TME). For this study, we conjugated the CH401 peptide-containing B-cell, helper T-cell, and cytotoxic T-cell epitopes of HER2-to the plant cowpea mosaic virus (CPMV) and bacteriophage Qβ to develop vaccines for HER2⁺ cancer. In vivo studies confirmed that the CPMV_CH401 i.t. therapeutic vaccine candidate was successful in CT26-HER2 and MC38-HER2 tumor models through the induction of IgG2a antibodies, upregulation of Th1 cytokines, and activation of Th1 cells. On the other hand, the Qβ_CH401 i.t. therapeutic vaccine candidate induced IgG1 antibodies and a Th1/2 balanced response, which did not result in potent anti-tumor efficacy. This study highlights that different VNP carriers are differential in immune modulation and that CPMV_CH401, but not Qβ_CH401, is effective as an i.t. vaccine. We also learned that the subcutaneous prophylactic immunization route leads to stronger humoral immunity but fails to modulate the TME, limiting the anti-tumor efficacy. This study highlights that, combined with the HER2 epitope, the i.t. therapeutic approach has powerful anti-tumor capabilities. It induces therapeutic HER2 antibodies, immunomodulation of the TME, and T-cell responses against the tumor, making this a robust active immunotherapy regimen.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2583553"},"PeriodicalIF":6.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745303","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":"Prostate tumor immune microenvironment changes following immunotherapy shared by patients who developed anti-tumor response or immune-related adverse events.","authors":"Ichwaku Rastogi, Douglas G McNeel","doi":"10.1080/2162402X.2025.2595788","DOIUrl":"10.1080/2162402X.2025.2595788","url":null,"abstract":"<p><p>Checkpoint inhibitors targeting PD-1/PD-L1 have revolutionized cancer immunotherapy, yet their efficacy in prostate cancer has been limited. We previously reported a clinical trial (NCT02499835) evaluating PD-1 blockade combined with an anti-tumor DNA vaccine, pTVG-HP (encoding prostatic acid phosphatase), in patients with metastatic castration-resistant prostate cancer. Decreases in serum prostate-specific antigen (PSA) levels were observed in 35% of patients, and 42% of patients developed immune-related adverse events (irAE). In long-term follow-up, any decrease in PSA or the development of an irAE was associated with prolonged overall survival (<i>p</i> = 0.009 or <i>p</i> = 0.006, respectively), suggesting a potential association between irAE and anti-tumor immunity. To evaluate this, tumor biopsies obtained pre- and post-treatment from 12 patients were evaluated by gene expression profiling and spatial protein analysis. Clinical responders (those with any decrease in PSA) presented with reduced checkpoint marker expression and increased expression of markers associated with dendritic cells, antigen presentation, and T-cell activation. These gene expression signatures highly overlapped with signatures from patients who experienced an irAE. Conversely, non-responders showed enrichment of immunosuppressive pathways, including elevated expression of VISTA and myeloid-derived suppressor cell (MDSC)-associated markers. Patients without irAE had increased expression of PARP. These findings suggest that patients experiencing irAEs can have immune responses to tumor irrespective of obvious anti-tumor efficacy, at least with these treatments, and underscore the importance of tumor-infiltrating professional antigen presenting cells and T-cell activation for successful immunotherapy. Moreover, our findings suggest that combining vaccines and PD-1 blockade with MDSC-targeting therapies, anti-VISTA, and/or anti-PARP therapies might be further explored.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2595788"},"PeriodicalIF":6.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726932","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":"Simultaneous secretion of a PD-L1 x 4-1BB bispecific antibody improves antileukemic efficacy of STAb-T cells secreting a CD19-specific T-cell engager.","authors":"Marina Gómez-Rosel, Laura Rubio-Pérez, Ivana Zagorac, Carmen Domínguez-Alonso, Laura Díez-Alonso, Oana Hangiu, Rocío Navarro, Raúl Torres-Ruíz, Sandra Rodríguez-Perales, Francisco J Blanco, Marta Compte, Luis Álvarez-Vallina, Belén Blanco","doi":"10.1080/2162402X.2025.2570224","DOIUrl":"10.1080/2162402X.2025.2570224","url":null,"abstract":"<p><p>Adoptive therapy with CAR-T cells and systemic administration of bispecific T-cell engagers (TCE) have achieved unprecedented success in the treatment of relapsed/refractory (R/R) B-cell malignancies. However, high relapse rates remain a major challenge. STAb (<b>S</b>ecretion of <b>T</b> cell-redirecting bispecific Antibodies)-T-cell immunotherapy represents a promising alternative by enabling both polyclonal T-cell recruitment and sustained bispecific antibody release. Here, we describe an evolution of STAb-T19 therapy, which has demonstrated superior outcomes to those of CAR-T-19 cells in preclinical models of B-ALL, on the basis of the simultaneous secretion of two bispecific antibodies: a CD19 × CD3 TCE and a PD-L1 × 4-1BB bsAb. The combined approach aims to increase the antitumor efficacy of STAb-T19 cells by blocking the PD-1/PD-L1 axis with conditional 4-1BB costimulation to ensure the long-term persistence of STAb-T cells. Preclinical data show that this combination improves cytotoxic activity and prolongs antileukemic efficacy compared with low-dose single STAb-T therapy. Our findings suggest that the integration of PD-L1 × 4-1BB bsAbs into STAb-T19 therapy may maximize efficacy, thereby opening a promising avenue to address resistance and relapse in B-ALL. Moreover, this approach may pave the way for the development of next-generation cell-based therapies for hematologic and solid malignancies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2570224"},"PeriodicalIF":6.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12562732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372458","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.2025.2600808","DOIUrl":"10.1080/2162402X.2025.2600808","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2600808"},"PeriodicalIF":6.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758036","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":"Membrane IL-18 identifies a human macrophage subset with distinct proteomic and functional traits.","authors":"Chiara Vitale, Andrea Petretto, Katia Cortese, Sonia Carta, Alessandra Dondero, Chiara Lavarello, Davide Cangelosi, Martina Morini, Francesca Bellora, Pietro Arnaldi, Fabrizio Loiacono, Santina Bruzzone, Francesco Piacente, Silvia Bruno, Martina Serra, Annamaria Pessino, Serafina Mammoliti, Alberto Garaventa, Massimo Conte, Massimo Locati, Giuseppe Danilo Norata, Marco Colonna, Eric Vivier, Cristina Bottino, Roberta Castriconi","doi":"10.1080/2162402X.2025.2571774","DOIUrl":"10.1080/2162402X.2025.2571774","url":null,"abstract":"<p><p>This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display heterogeneous FOLR2 expression, distinguishing distinct cell subsets with possibly different functions. Accordingly, in primary neuroblastomas, transcriptional signatures associated with mIL-18 expression show different prognostic values. Our data show that mIL-18+ macrophages, which are predominant across the tumor microenvironment, exhibit previously undetected heterogeneity, potentially impacting tumor progression in a variable manner.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2571774"},"PeriodicalIF":6.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12599568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453732","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}