Oncoimmunology最新文献

{"title":"Store-operated calcium signaling modulators improve a dendritic cell-based vaccine against melanoma.","authors":"María Cruz Cobo, Laure Garnier, Marion Mandavit, Maral Azam, Isabelle Dentand Quadri, Julien Angelillo, Dale Brighouse, Mathilde Bausart, Valérie Dutoit, Achille Schild, Valeria M Oliva, Martin Lochner, Bénédicte Manoury, Stéphanie Hugues, Paula Nunes-Hasler","doi":"10.1080/2162402X.2026.2723541","DOIUrl":"10.1080/2162402X.2026.2723541","url":null,"abstract":"<p><strong>Summary: </strong>Cruz Cobo et al. identify small molecules that reprogram dendritic cells toward an immuno-stimulating secretory phenotype, revealing endoplasmic reticulum calcium signaling as a druggable axis to boost vaccine-based and T cell-mediated cancer immunotherapies. The study links broad changes in calcium-induced secretion to improved immune activation and therapeutic potency.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2723541"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851662","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":"A novel oncolytic peptide synergizing with immunotherapy.","authors":"Guido Kroemer, Xiaolian Deng, Baldur Sveinbjørnsson, Oliver Kepp","doi":"10.1080/2162402X.2026.2740845","DOIUrl":"10.1080/2162402X.2026.2740845","url":null,"abstract":"<p><p>In a recent paper published in Nature, Yuan et al. described an acid-responsive membranolytic peptide that temporally separates lysosomes from later plasma membrane rupture, thereby converting oncolysis into immunogenic cell death. This elegant design permits systemic administration, elicits antigen-specific immunity, and sensitizes tumors to programmed death ligand 1 blockade with remarkably limited toxicity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2740845"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116728","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":"Irradiated dendritic cell subsets retain key immune capabilities and anti-tumor immunity is not strictly dependent on cDC1.","authors":"Teresa Irianto, Ann-Sophie Flohr, Clara Reichardt, Ateeqa Ghuias, Lisa Weissmann, Detlef Freitag, Lukas Amon, Christian H K Lehmann, Diana Dudziak, Kai Hildner, Stefanie Corradini, Benjamin Frey, Udo S Gaipl, Michael Rückert","doi":"10.1080/2162402X.2026.2743436","DOIUrl":"https://doi.org/10.1080/2162402X.2026.2743436","url":null,"abstract":"<p><p>Radiotherapy can enhance anti-tumor immunity by modulating the tumor microenvironment. However, its direct effects on dendritic cells (DCs) as key antigen-presenting cells remain poorly studied. Although DCs are considered relatively radioresistant, their functional capacity following irradiation is controversial and likely subset-dependent. In this study, we systematically analyzed the radiosensitivity and post-irradiation functional capacity of murine bone marrow-derived conventional type 1 DCs (cDC1s), which play a pivotal role in initiating CD8⁺ T cell-mediated anti-tumor immunity, conventional type 2 DCs (cDC2s), and monocyte-derived DCs (MoDCs) <i>in vitro</i>. After irradiation, DC viability and surface marker expression were assessed. To evaluate functional competence, DCs were stimulated with high hydrostatic pressure-inactivated tumor cells in combination with the adjuvants poly I:C and α-CD40 as a model system for therapeutic tumor vaccination, and the phagocytic activity, activation, and cytokine/chemokine secretion of the DCs were analyzed. DC radiosensitivity depended strongly on both the subset and maturation state, with mature DCs showing higher radioresistance than their immature counterparts, and with immature cDC1s being particularly more susceptible. Nevertheless, surviving DCs retained their ability to phagocytose tumor cells and, upon stimulation, upregulate activation- and migration-associated markers and secrete cytokines and chemokines. <i>In vivo</i>, radio-immunotherapy promoted DC migration to the tumor-draining lymph node and induced DC activation, as indicated by elevated concentrations of DC-related cytokines in the peripheral blood. Within a fixed radiotherapy plus checkpoint inhibition regimen, tumor growth delay was largely preserved in Batf3^-/- mice, lacking the cDC1 subset. Collectively, irradiation does not abrogate DC function, and anti-tumor immunity in radio-immunotherapy does not strictly require cDC1s.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2743436"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149301484","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":"Unlocking the therapeutic potential of immuno-radiotherapy: insights from preclinical and clinical research.","authors":"M M Cogels, A de Caluwé, L Buisseret, S Penninckx","doi":"10.1080/2162402X.2025.2608436","DOIUrl":"10.1080/2162402X.2025.2608436","url":null,"abstract":"<p><p>The immunomodulatory potential of radiotherapy provides a strong rationale for its combination with immunotherapies and other immunostimulatory agents. However, current combinations yield suboptimal clinical benefits. As the mechanisms behind radiotherapy-induced immunomodulation are gradually unraveled, various key factors have been identified as critical modulators of this process, opening new possibilities for adapting radiotherapy to immunotherapy. Here, we discuss seven factors: dose‒fractionation regimens of radiotherapy (RT), sequence and timing of RT and immunotherapy, radiation field, type of ionizing radiation, normal tissue effects, choice of the lesion to irradiate and identification of biomarkers. Preclinical and clinical studies on the combination of immunotherapy and radiotherapy are discussed, novel immunotherapeutic approaches are highlighted and improvements in study design are suggested.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2608436"},"PeriodicalIF":6.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12778880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906970","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 double face of IL-1β in lung cancer.","authors":"Cédric Rébé, Anaïs Perrichet, François Ghiringhelli","doi":"10.1080/2162402X.2026.2622661","DOIUrl":"10.1080/2162402X.2026.2622661","url":null,"abstract":"<p><p>Interleukin (IL)-1β is known to promote lung cancer growth in both humans and mice. However, in the context of the current standard of care, which includes chemotherapy and immune checkpoint inhibitors, IL-1β can overcome resistance.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2622661"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114685","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":"<i>In vitro</i> generated macrophages reflect the immunosuppressive phenotype of <i>in vivo</i> glioblastoma-associated macrophages.","authors":"Matthew Nazzaro, Elaine R Mardis, Mykyta Artomov, Ella Juenger, Justin Lyberger, Mark Damante, Gregory Behbehani, Susobhan Sarkar, Prajwal Rajappa","doi":"10.1080/2162402X.2025.2610562","DOIUrl":"10.1080/2162402X.2025.2610562","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common primary central nervous system tumor with a dismal prognosis and limited treatment options. Recent success utilizing immunotherapies for treating other solid tumors have been largely unsuccessful in GBM. One of the primary mechanisms of GBM immunotherapeutic resistance is because of excessive infiltration of myeloid cells that create an immunosuppressive tumor microenvironment (TME). Among these infiltrating myeloid cells, tumor-associated macrophages (TAMs), comprise a substantial portion of the TME and are associated with poor prognosis in GBM patients. Researchers have only recently begun to dissect the dynamics and complexity of TAMs. However, reliable and reproducible translational methods for generating GBM TAMs <i>in vitro</i> are lacking. Here, we have investigated an <i>in vitro,</i> reproducible murine-based model for bone marrow-derived, glioma-educated macrophages (gTAMs) and performed rigorous analysis to expand our understanding of gTAMs to provide a validated tool for investigating therapeutic response.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2610562"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047314","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":"Contrasting functions of CD73 and adenosine in CD8+ T-cell exhaustion during antitumor immunity.","authors":"Juan Saavedra-Almarza, Solange Gouët, Felipe Malgue, Catalina Bascuñan, Andrés Hernández-Oliveras, Joaquín De la Rosa, Javiera Reyes-Alvarez, Camilo Villaman, José Corrales-Bermúdez, Justine Castañeda, Moira García-Gómez, Alberto J M Martin, Álvaro Lladser, Mario Rosemblatt, María Rosa Bono, Daniela Sauma","doi":"10.1080/2162402X.2026.2642458","DOIUrl":"10.1080/2162402X.2026.2642458","url":null,"abstract":"<p><p>T-cell exhaustion is a state of functional decline in T cells, driven by chronic antigen exposure and inhibitory signals within the tumor microenvironment. Exhausted CD8+ T cells (Tex) derive from precursor exhausted T cells (Tpex), a self-renewing population responsible for the proliferative burst in anti-PD-1 therapies. Exhausted T cells are exposed to adenosine in the tumor, yet the role of the CD73/adenosine axis and Tpex/Tex differentiation remains unclear. Using an <i>in vitro</i> model for CD8+ T-cell exhaustion, we found that CD73 expression increased during Tpex formation and that its expression was negatively correlated with Tex generation. CD73-deficient OT-I cells (OT-I/CD73KO) showed impaired activation and reduced progression to Tex. Moreover, we demonstrated that CD73 promotes transcriptional expression of the adenosine receptor A2A (A2AR). RNA-seq analysis of exhausted OT-I/CD73KO cells revealed a more stem-like transcriptomic profile and enrichment in genes associated with the immune response compared to their OT-I counterparts. <i>In vivo</i>, the cotransfer of naïve OT-I/CD73KO and OT-I antigen-specific CD8⁺ T cells into tumor-bearing mice resulted in increased Tpex frequency and numbers among OT-I/CD73KO cells in tumors. Conversely, <i>in vitro</i> exhaustion in the presence of A2AR agonists decreased Tex frequency and activation/exhaustion markers, while increasing CD73 and CD62L, which are markers associated with stemness. Supporting this, A2AR blockade with SYN115 in tumor-bearing mice reduced Tpex markers and increased Tex differentiation. Altogether, our data suggest that CD73 promotes Tpex-to-Tex differentiation, whereas adenosine A2AR signaling supports Tpex maintenance in the tumor microenvironment.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2642458"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445645","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":"Characterization of persistent HPV-specific activated T cells in head and neck squamous cell carcinoma.","authors":"Hiromasa Ishihara, Hirofumi Shibata, Daisuke Muraoka, Ayako Demachi-Okamura, Takanari Okamoto, Ryo Mizuta, Yasunori Fukushima, Yusuke Sugita, Aiko Ogasawara, Reina Nishida, Shintaro Beppu, Hoshino Terada, Daisuke Nishikawa, Hidenori Suzuki, Katsuhiro Masago, Eiichi Sasaki, Noriaki Sakakura, Rui Yamaguchi, Nobuhiro Hanai, Takenori Ogawa, Hirokazu Matsushita","doi":"10.1080/2162402X.2026.2707808","DOIUrl":"10.1080/2162402X.2026.2707808","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC) generally has favorable outcomes yet remains prone to late recurrence. Durable control likely depends on persistent tumor-specific CD8+ T cells, but their persistence and function in metastasis are poorly understood.</p><p><strong>Methods: </strong>We integrated bulk RNA sequencing (<i>n</i> = 56) with single-cell RNA and paired T-cell receptor (TCR) sequencing of tumor-infiltrating CD8+ T cells (<i>n</i> = 4), including a longitudinal primary-lung metastasis pair obtained three years after curative therapy. HPV genotyping, HLA typing, epitope prediction, and NFAT-reporter Jurkat-luciferase assays were used to identify and functionally validate HPV16 E6/E7-specific TCRs. Repertoire tracking and single-cell/bulk transcriptomics were evaluated.</p><p><strong>Results: </strong>HPV + tumors showed higher inferred CD8+ T cell infiltration and more favorable prognosis than HPV- tumors. Single-cell analysis revealed oligoclonally expanded exhausted clusters enriched in HPV tumor-specific CD8+ T cells. We isolated and functionally validated nine patient-derived HPV16 E6/E7-specific TCRs. High-avidity receptors recognizing an alternatively spliced region in E6 (aa 49-110; E6*) persisted in metastatic lesions, whereas lower-avidity clones, including an E7_11-19-specific TCR currently under clinical investigation, were lost. Compared with the primary tumor, metastatic lesions showed reduced stem-like/TCF7-associated CD8+ T-cell populations and enrichment of HPV-specific CD8+ T cells expressing <i>KLRB1</i> and <i>ZNF683</i>, consistent with a tissue-adapted TRM-like transcriptional state with inhibitory signaling features.</p><p><strong>Conclusions: </strong>High-avidity, <i>KLRB1</i> + HPV-specific CD8+ T cells represent a persistent effector subset with prognostic and therapeutic relevance to HPV + OPSCC. Their persistence in metastatic lesions and association with reduced recurrence risk support further investigation of <i>KLRB1</i>-associated HPV-reactive T-cell states as biomarkers and immunotherapeutic targets.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2707808"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148594270","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":"Integrating tumor and immune cell transcriptomics to predict immune checkpoint inhibitor primary resistance in metastatic melanoma.","authors":"Juan Luis Onieva, Elisabeth Pérez-Ruiz, Ville Vilkki, Miguel Berciano-Guerrero, Laura Figueroa-Ortiz, Manuel Zalabardo, Beatriz Martínez-Gálvez, Isabel Barragán, Antonio Rueda-Domínguez","doi":"10.1080/2162402X.2026.2650234","DOIUrl":"10.1080/2162402X.2026.2650234","url":null,"abstract":"<p><p>The emergence of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape of metastatic melanoma. However, despite its success, reliable biomarkers for predicting primary resistance are not available in clinical practice. This study seeks to identify predictors of primary resistance based on novel gene expression signatures. The transcriptomic profile of the tumor microenvironment was analyzed using tissue samples from 46 metastatic cutaneous melanoma patients collected prior to the initiation of ICIs therapy. A primary resistance predictive model was trained with the Discovery FFPE RNA-seq subcohort and validated using an independent external cohort of 54 samples. Additionally, liquid biopsy samples from peripheral blood mononuclear cells were analyzed in 8 patients using single-cell RNA sequencing (scRNA-seq) and in 46 patients using flow cytometry. We identified an 82-gene transcriptomic signature composed of tumor- and immune-related genes that stratifies metastatic cutaneous melanoma patients based on primary resistance to ICIs, with key markers including <i>CXCL13, WDR63, MZB1, FDCSP, IGKC</i> and <i>GRIK3</i>. This signature achieved an AUC of 0.814. Immune deconvolution guided by scRNA-seq revealed four immune cell subsets (Plasma cells, Pre-B cells, memory CD4⁺ T cells, and naive CD4⁺ T cells) as prognostic indicators of resistance. We propose a transcriptomic biomarker signature that accurately predicts primary resistance to ICIs in metastatic cutaneous melanoma. Through the integration of immune deconvolution with circulating immune cell profiles, we derived an ImmuneSignature linked to patient survival. By combining these approaches, we provide a framework for enhancing the prediction of immunotherapy outcomes and offer a novel strategy for identifying therapeutic targets to overcome resistance.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2650234"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582049","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":"CXCL13-expressing CD4⁺ T cells coordinate the lymphocytes triad to promote the anti-tumor immunity in NSCLC.","authors":"Danping Liu, Jiajun Luo, Wei Guo, Junrui Ma, Xiaobao Yang, Yihan Xia, Pu Li, Dakang Xu, Zhidong Gu","doi":"10.1080/2162402X.2026.2684116","DOIUrl":"10.1080/2162402X.2026.2684116","url":null,"abstract":"<p><p>CD4⁺ T cells are indispensable for CD8⁺ T cells-mediated anti-tumor immunity, while little is known about how CD4⁺ T cells coordinate with other cells to promote CD8⁺ T cells activity. In this study, by coupling single-cell RNA sequencing (scRNA-seq) with multiplex immunohistochemistry staining (mIHC), CXCL13-expressing CD4⁺ T cells were explored to recruit CXCR5⁺ B cells to form CXCL13⁺CD4⁺ T cells:: CXCR5⁺ B cells:: CD8⁺ T cells triad, promoting the anti-tumor immunity and heralding a favorable prognosis. A CXCL13-expressing subset of CD4⁺ T cells was identified to be associated with better prognosis and tumor-reactive hallmarks. The further cell types interaction analysis revealed a specific interaction between CXCL13⁺CD4⁺ T cells and CXCR5⁺ B cells in comparison with other cell types. The mIHC verified that an elevated level of CXCR5⁺ B cells infiltration in the proximity of CXCL13⁺CD4⁺ T cells. The subsequent Entropy analysis, which characterizes the colocalization among more than two cell types, was employed to reveal the spatial distribution pattern. The results revealed that CXCL13⁺CD4⁺ T cells and CXCR5⁺ B cells co-localized with cytotoxic CD8⁺ T cells, forming a functional lymphocyte triad, whose existence heralded a better prognosis. Collectively, by integrating scRNA-seq with mIHC, we demonstrated that the recruitment of CXCR5⁺ B cells by neoantigen reacting to CXCL13⁺CD4⁺ T cells through CXCL13-CXCR5 signaling contributed to the lymphocyte triad, leading to an enhanced anti-tumor immunity and heralding a favorable prognosis in non-small-cell lung cancer (NSCLC).</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2684116"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212899","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}