Oncoimmunology最新文献

{"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":"Human cDC1 enhance cytotoxic function of CD226+ terminally exhausted tumor-infiltrating lymphocytes.","authors":"Liam O'Brien, Irina Buckle, Ingrid M Leal-Rojas, Nikita Rosendahl, Kristen J Radford","doi":"10.1080/2162402X.2025.2521391","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2521391","url":null,"abstract":"<p><p>Prevention or reversal of T cell exhaustion is a major objective of cancer immunotherapy. However, few models exist to generate, characterize and modulate exhausted human T cells, particularly within solid tumors <i>in vivo</i>, which likely hampers the discovery and translation of novel therapeutics. In this study we describe a humanized mouse model where functional human CD8+ T cells specific for the tumor antigen NY-ESO-1 develop <i>in vivo</i> from human CD34+ hematopoietic stem cells genetically modified to express a HLA-A *0201-restricted NY-ESO-1 specific T cell receptor (TCR). HLA-A *0201+ NY-ESO-1+ expressing A375 melanoma tumors engrafted in these mice and were refractory to treatment with anti-PD-1 despite being infiltrated with NY-ESO-1 specific T cells. Tumor-Infiltrating Lymphocytes (TIL) upregulated tissue resident memory (TRM) markers CD103 and CD69 along with exhaustion markers PD-1, TIGIT, and CD39 relative to T cells from other organs. Further, TILs failed to secrete cytokines TNF and IFNγ following <i>in vitro</i> stimulation with conventional Type I Dendritic Cells (cDC1), indicative of terminal exhaustion. However, cDC1 stimulation of the terminally exhausted NY-ESO-1 specific TILs led to enhanced tumor killing that was associated with increased CD107a and Granzyme B expression that was restricted to a subset of CD226+ NY-ESO-1 specific TILs. These findings establish a novel platform to investigate T cell exhaustion in human tumors and suggest a role for cDC1 in enhancing terminally exhausted TIL cytotoxic function.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2521391"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477390","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":"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":"Tumor-infiltrating B cells produce tumor-specific antibodies and may contribute to suppressing tumor in head and neck squamous cell carcinoma.","authors":"Junsei Sameshima, Hu Chen, Naoki Kaneko, Lijing Yan, Shiho Yokomizo, Tomoki Sueyoshi, Haruki Nagano, Taiki Sakamoto, Shoichi Tanaka, Yasuyuki Maruse, Taichi Hattori, Ryoji Kitamura, Yoshikazu Hayashi, Takashi Maehara, Shinsuke Fujii, Tamotsu Kiyoshima, Thomas Guy, Zivile Giedraityte, Wataru Kumamaru, Masafumi Moriyama, Shintaro Kawano","doi":"10.1080/2162402X.2025.2543019","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2543019","url":null,"abstract":"<p><p>The involvement of T cells, particularly cytotoxic T cells, in tumor immunity has been reported, but the roles of B cells and antibodies in tumor immunity remain unclear. Previous studies have primarily focused on circulating B cells in the blood, with limited investigation of tumor-infiltrating B cells (TIL-Bs) and their secreted antibodies in head and neck squamous cell carcinoma (HNSCC) tissue. This study aimed to clarify TIL-Bs' role in HNSCC through comprehensive analyses including single-cell RNA sequencing of 68 cases, B-cell receptor repertoire analysis, multiplex immunofluorescence staining, and spatial transcriptomics analysis of resected HNSCC specimens. We identified CXCL13⁺CD4⁺ T cells that attract B cells, along with TIL-Bs at various differentiation stages, showing clonal expansion of antibody-secreting cells (ASCs). These ASCs exhibited a low somatic hypermutation frequency, indicating that they are likely activated through extrafollicular response rather than germinal center response. Protein microarrays with recombinant antibodies mimicking TIL-Bs secretory antibodies and serum antibodies revealed several antigens highly expressed in tumor cells. These antigens demonstrated higher expression in tumor cells than normal epithelial cells in the resected HNSCC specimens. Tissue analysis indicated that antibodies binding to these antigens are recognized by macrophage and NK cells with Fc receptors, potentially enhancing tumor immunity. The existence of tumor-infiltrating ASCs showed correlation with favorable prognosis. This study demonstrated for the first time that expanded TIL-Bs produce antibodies and likely contribute to tumor elimination by activating tumor immunity in HNSCC tissues. This novel insight could lead to radically new therapies targeting B cells.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2543019"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800597","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":"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":"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":"Chemoimmunomodulation in triple negative breast cancer: a key to maximizing anti-PD-1 chemoimmunotherapeutic efficacy.","authors":"Mohammed O Gbadamosi, Elizabeth Molchan, Mariana S Makarem, Kennedy L Coleman, Alyssa C Ohaegbulam, Kathleen H Streeks","doi":"10.1080/2162402X.2025.2527303","DOIUrl":"10.1080/2162402X.2025.2527303","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is among the aggressive subtype of breast cancer with a distinct lack of viable treatment strategies and poor clinical outcomes. Anti-PD-1 chemoimmunotherapy (CIT), which leverages the vast array of immunomodulatory effects induced by chemotherapeutic agents to potentiate anti-PD-1 blockade, has emerged as a promising standard-of-care treatment option. However, the clinical benefit from anti-PD-1 CIT has been limited and heterogeneous in advanced TNBC. One of the major reasons for these limitations is the lack of understanding regarding the immunomodulatory properties of chemotherapeutics with respect to individual patients. In this review, we discuss the immunomodulatory properties of first-line chemotherapeutic agents in TNBC and the potential benefits that optimizing chemoimmunomodulation offers toward maximizing CIT efficacy in TNBC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2527303"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592699","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":"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}