Oncoimmunology最新文献

{"title":"Sialic acid <i>cis</i>-ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity.","authors":"Jesper van Eck van der Sluijs, Anne H C Valk, Eline J H van Houtum, Esther D Kers-Rebel, Maaike Looman, Willemijn Hobo, Anna E Marneth, Harry Dolstra, Lune van den Boogaard, Christian Büll, Lenneke A M Cornelissen, Gosse J Adema","doi":"10.1080/2162402X.2026.2649988","DOIUrl":"10.1080/2162402X.2026.2649988","url":null,"abstract":"<p><p>The glyco-immune checkpoints Siglec-7 and Siglec-9 have received considerable interest as targets for cancer immunotherapy. How Siglec-7/9-sialic acid <i>cis</i>-interactions on immune cells influence <i>trans</i>-signaling induced by tumor cells and whether Siglec-7 and -9 co-blockade can enhance immune effector cell function are key questions for clinical translation. We developed and applied single and dual Jurkat/MA NFAT-luciferase reporter cells expressing wild-type or mutant chimeric Siglec-7 and/or -9. <i>Cis</i>-interactions on these Jurkat/MA reporter cells prevented Siglec-7 and -9 signaling induced by <i>trans</i>-ligands, i.e. on tumor cells. In Jurkat/MA cells expressing both receptors, Siglec-7/9 co-inhibition was essential to fully block receptor signaling. Extrapolating our findings to human primary cells, NK cell-mediated killing of melanoma and acute myeloid leukemia (AML) cell lines and patient-derived AML cells was increased upon Siglec-7 and/or -9 blockade. Importantly, co-blockade was superior to single blocking strategies and the effects were most pronounced when <i>cis</i>-ligands were removed from the NK cell' surface using sialidase. Further diving into <i>cis</i>-ligand dynamics on primary human NK cells, physiological NK cell activation with IL-2 or IFN-<i>α</i> or IL-15/IL-2-induced proliferation was shown to significantly downregulate Siglec-7 and -9 <i>cis</i>-ligand expression. Moreover, Siglec-7 and -9 ligands were progressively downregulated with each round of NK cell division. Taken together, our findings highlight the important role of <i>cis</i>-interactions in regulating <i>trans</i>-interactions and emphasize the potential of simultaneously blocking Siglec-7 and -9 for clinical applications. These insights may guide the design of next-generation Siglec-targeted immunotherapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2649988"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610469","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-educated macrophages promote cytokine-driven lung colonization in triple-negative breast cancer.","authors":"María Rosado-Sanz, Nuria Martínez-Alarcón, Michaël H Meel, Sergio Rius-Perez, Zoey J Tolboom, Carmen Salvador-Coloma, Rebeca Burgos-Panadero, Esther Coronado, Guillermina Montoliu, Eloi Casals, Anna Esteve-Codina, Francisco Ripoll, Ana Santaballa, Jaime Font de Mora","doi":"10.1080/2162402X.2026.2687381","DOIUrl":"10.1080/2162402X.2026.2687381","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) remains one of the most lethal breast cancer subtypes, driven by early dissemination and resistance to therapy. Here, we reveal a macrophage-centered cytokine circuit that fuels TNBC metastasis and immune evasion. Tumor cells reprogram naïve macrophages into tumor-associated macrophages (TAMs) that secrete CCL3, CCL4, CXCL2, and IL-1β, collectively promoting epithelial-to-mesenchymal transition, migration, transendothelial invasion, and lung colonization. These TAMs, in turn, convert naïve CD4⁺ T cells into FOXP3⁺ Tregs, establishing a self-reinforcing immunosuppressive niche. Pharmacological inhibition of CCR5, CXCR2, and IL1R1 with maraviroc, navarixin, and anakinra, respectively, disrupted this cytokine axis, suppressing metastatic colonization <i>in vivo</i>. Our findings reveal that blocking cytokine receptor signaling disrupts the pro-metastatic crosstalk between macrophages and TNBC cells, offering a clinically actionable strategy to restrain metastasis and overcome therapy resistance in TNBC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2687381"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148279512","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":"Efficacy and safety of cabozantinib plus nivolumab in advanced non-clear cell renal cell carcinoma: a nationwide multicenter study.","authors":"Chang Gon Kim, Junkyu Kim, In-Ho Kim, Eun Hee Jung, Hyeon-Su Im, Byung Woog Kang, Ji Hyun Park, Joo-Hwan Park, Jungmin Jo, Eo Jin Kim, Seung Hoon Beom, Sun Young Rha, Se Hyun Kim, Inkeun Park, Se Hoon Park, Jae-Lyun Lee, Sang Joon Shin","doi":"10.1080/2162402X.2026.2694175","DOIUrl":"10.1080/2162402X.2026.2694175","url":null,"abstract":"<p><p>Non-clear cell renal cell carcinoma (nccRCC) represents a biologically heterogeneous group of tumors for which optimal systemic treatment strategies remain poorly defined despite recent therapeutic advances. To address this gap, we evaluated the clinical activity and safety of cabozantinib plus nivolumab in patients with advanced nccRCC. In this nationwide, multicenter retrospective cohort study conducted in the Republic of Korea, 62 patients received the combination across multiple lines of therapy, with most treated in the first-line setting. Papillary RCC was the most common histologic subtype (50.0%), followed by <i>FH</i>-deficient (22.6%), <i>TFE3</i>-rearranged (9.7%), chromophobe (6.5%), collecting duct (6.5%), and unclassified tumors (4.8%). With a median follow-up of 22.2 months (95% confidence interval [CI], 15.4-29.1), the objective response rate (ORR) was 45.2% (95% CI, 32.4-57.9) and the disease control rate (DCR) was 93.6% (95% CI, 87.3-99.8). Responses were seen across histologic subtypes (ORR = 48.4% in papillary, 50.0% in <i>FH</i>-deficient, 50.0% in <i>TFE3</i>-rearranged, 25.0% in chromophobe, 25.0% in collecting duct, and 33.3% in unclassified tumors; <i>P</i> = 0.876). Median progression-free and overall survival were 9.7 months (95% CI, 7.7-11.6) and 22.0 months (95% CI, 15.2-28.7), respectively. Grade 3-4 treatment-emergent adverse events occurred in 46.8% of patients, and treatment discontinuation due to toxicity was reported in 6.5%. These findings demonstrate that cabozantinib plus nivolumab provides clinically meaningful and durable antitumor activity with manageable toxicity across diverse histologic subtypes in advanced nccRCC, supporting further prospective evaluation of cabozantinib plus nivolumab in advanced nccRCC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2694175"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347023","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":"Unveiling the immune microenvironment in sinonasal intestinal type adenocarcinoma: new arguments for immunotherapy.","authors":"Charles Lépine, Cécile Deleine, Richard Danger, Laura Do Souto Ferreira, Elisabeth Nguyen, Marie-Anne Vibet, Olivier Malard, Nadine Gervois, Karine Renaudin, Anne Jarry","doi":"10.1080/2162402X.2026.2725500","DOIUrl":"10.1080/2162402X.2026.2725500","url":null,"abstract":"<p><p>Sinonasal intestinal-type adenocarcinoma (ITAC) is a rare malignancy strongly associated with occupational exposure to wood dust that shares morphological and molecular similarities with colorectal adenocarcinoma. Standard treatments offer limited benefit for advanced or recurrent disease. It is therefore necessary to develop other strategies, such as immunotherapies, which require a better understanding of the tumor immune microenvironment, are needed. In this study, we investigated the immune microenvironment of ITACs (n<i>=59</i>), focusing on tumor-infiltrating T lymphocytes (TILs) and macrophages, <i>in situ</i> using immunohistochemistry, <i>ex vivo</i> by multiparametric flow cytometry, as well as by transcriptomic profiling. High CD8⁺ T-cell densities were associated with significantly improved disease-free and overall survival and emerged as an independent prognostic factor. These TILs express immune checkpoints (IC), the most highly expressed being PD1, TIGIT, and TIM-3. Furthermore, TIM-3 was not only expressed by TILs but also by immunoregulatory macrophages, and may represent an important immune escape mechanism in ITACs, since TIM-3 blockade in patient-derived explants led to increased tumor cell apoptosis. Tumor cells strongly expressed CD155 (TIGIT ligand) but not PDL1 (PD1 ligand); however expressed by myeloid cells. Finally, transcriptomic analyses identified one cluster displaying features of \"hot tumors\" characterized by adaptive immune activation, a better prognosis, and a higher immunotherapy response score, and another cluster with features of \"cold tumors\". These first exploratory and descriptive findings in ITACs provide a rationale for further investigations using ex vivo and in vivo models to evaluate the therapeutic potential of immunotherapies in these rare cancers.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2725500"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888981","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 tumor-selective membrane-associated PCNA enables selective antibody-drug conjugate therapy.","authors":"Muhammad Abu Ahmad, Nir Miriam Ungar-Malma, Alon Naumchik, Noy Machluf-Katz, Olga Radinsky, Sarah Adi Eisdorfer, Abedallh Gara, Yosef Istoyler, Irit Alon, Daniel Sevilla-Sanchez, Kerry S Campbell, Bar Kaufman, Moshe Elkabets, Angel Porgador","doi":"10.1080/2162402X.2026.2740432","DOIUrl":"10.1080/2162402X.2026.2740432","url":null,"abstract":"<p><p>Membrane-associated proliferating cell nuclear antigen (mPCNA) is an attractive tumor-selective antigen for antibody-drug conjugate (ADC) development. We generated a chimeric IgG1 ADC, RC14-MMAE, to exploit three key properties of mPCNA that support its use as an efficient delivery platform. First, flow-cytometric and imaging analyses show abundant mPCNA surface expression on multiple tumor cell lines and in JIMT1 xenografts, providing accessible epitopes for binding. Second, comparative profiling against non-malignant counterparts and normal mouse tissues reveals minimal or undetectable mPCNA at the plasma membrane of healthy cells, indicating a sharp tumor-normal differential expected to limit off-tumor targeting and improve the therapeutic window. Third, live-cell internalization assays demonstrate that RC14 rapidly accumulates in LAMP1-positive lysosomes after engaging mPCNA, confirming efficient trafficking along the endolysosomal pathway required for protease-mediated cleavage of the valine-citrulline linker and release of monomethyl auristatin E (MMAE). Consistent with this target profile, RC14-MMAE exhibits potent antigen-dependent cytotoxicity in mPCNA-positive tumor models in NSG mice, favorable pharmacokinetics, sustained payload retention in serum, robust <i>in vivo</i> antitumor activity with limited overt toxicity, and a significantly increased fraction of F4/80⁺ tumor-infiltrating myeloid cells within dissociated tumors. These findings establish mPCNA as a functionally validated, tumor-selective internalizing target and support RC14-MMAE as a first-in-class mPCNA-directed ADC with broad translational potential.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2740432"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185321","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":"Enhancing immunogenic cell death by targeting the GPX4-ZP3 immune checkpoint.","authors":"Daolin Tang, Rui Kang, Peng Liu, Guido Kroemer","doi":"10.1080/2162402X.2026.2624244","DOIUrl":"10.1080/2162402X.2026.2624244","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2624244"},"PeriodicalIF":6.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120710","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":"Clinical outcomes and blood-based biomarkers across two SABR-treated metastatic settings: oligoprogression under immune checkpoint inhibition and oligometastatic disease.","authors":"Juan Zafra-Martin, Juan Luis Onieva, Herminda Jimenez-Rodriguez, Beatriz Martinez, Laura Figueroa-Ortiz, Alicia Roman, Rafael Ordoñez, Elisabeth Pérez-Ruiz, Andres Mesas, Jose Miguel Jurado, Barbara Salas, Elisa Salcedo, Rodolfo Chicas-Sett, Antonio Rueda-Dominguez, Isabel Barragan","doi":"10.1080/2162402X.2026.2739021","DOIUrl":"10.1080/2162402X.2026.2739021","url":null,"abstract":"<p><p>Stereotactic ablative radiotherapy (SABR) may extend the clinical benefit of immune checkpoint inhibitors (ICI) in patients with oligoprogressive disease. However, individual benefit varies, and validated biomarkers to guide patient selection are lacking. We hypothesize that cell-free DNA (cfDNA) and the neutrophil-to-lymphocyte ratio (NLR) may be associated with outcomes after SABR in this setting. This prospective observational study included patients with oligoprogression under ICI therapy who received concomitant SABR to all oligoprogressive lesions (cohort A). Cohort B was a parallel biomarker cohort of oligometastatic patients receiving only SABR. Blood samples were collected before SABR (T1), after the first (T2) and last (T3) fractions, and two months after SABR (T4). The objective response rate (ORR) was evaluated by iRECIST in all lesions. Prespecified cfDNA and NLR time points were explored in relation to modified progression-free and overall survival (OS). We assessed 104 patients. With a median follow-up of 12 months, ORR was 59% in cohort A and 65% in cohort B. In cohort A, cfDNA <0.37 ng/µL at T3 was associated with improved 1-year OS (91% vs 62%, <i>p</i> = 0.031), while NLR <1.8 at T1 was associated with improved 1-year OS (100% vs 70%, <i>p</i> = 0.01). In cohort B, a >3% increase in cfDNA from T2 to T4 and NLR <4 at T4 were associated with improved OS. These findings support further evaluation of cfDNA and NLR as accessible biomarkers for patient stratification in oligoprogressive disease treated with SABR while maintaining an ICI.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2739021"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070219","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":"Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer.","authors":"Mehmet Haluk Yucel, Maral Martin Mildanoglu, Ebru Engin Delipoyraz, Hakan Ozcelik, Erdem Sunger, Sena Fidan, Cihat Terzioglu, Tansel Cakir, Harun Muglu, Burcin Cakan Demirel, Jamshid Hamdard, Yasin Kutlu, Ozgur Acıkgoz, Mesut Seker, Ahmet Bilici","doi":"10.1080/2162402X.2026.2738262","DOIUrl":"10.1080/2162402X.2026.2738262","url":null,"abstract":"<p><p>Growing evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors across multiple malignancies. However, evidence in extensive-stage small cell lung cancer (ES-SCLC) remains limited to a single East Asian cohort, and independent validation in other populations is lacking. We conducted a retrospective single-center cohort study of 107 patients with ES-SCLC treated with first-line platinum-etoposide plus atezolizumab or durvalumab. The time of day of administration (ToDA) was defined as the median start time of the first four immunotherapy infusions, and patients were categorized according to the cohort median ToDA. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The cohort median ToDA was 11:54. Patients treated before the median ToDA had significantly longer median PFS (9.07 vs. 7.23 months, <i>p</i> = 0.002) and OS (21.17 vs. 11.43 months, <i>p</i> = 0.002) than those treated later. In multivariable Cox regression analysis, later administration remained independently associated with shorter PFS (adjusted HR 1.63, 95% CI 1.03-2.58; <i>p</i> = 0.038) and OS (adjusted HR 1.65, 95% CI 1.00-2.71; <i>p</i> = 0.049), whereas objective response rates, treatment-related toxicity, and immune-related adverse events were comparable between groups. Morning administration of first-line chemoimmunotherapy was associated with significantly longer survival without increased toxicity in patients with ES-SCLC. These findings support growing evidence that circadian timing may influence immune checkpoint inhibitor efficacy and warrant prospective evaluation of treatment timing as a readily modifiable strategy to optimize immunotherapy delivery.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2738262"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13618832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040644","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":"Sequential axitinib and survivin vaccination unlock curative PD-1 immunotherapy in renal carcinoma.","authors":"Fanny Méjean, Thi Tran, Maya Merabet, Alain Gey, Andyara Munoz, Benjamin Morin, Ali Bal, Morgane Bourhis, Nesrine Mabrouk, Magali Terme, Eric Tartour, Corinne Tanchot","doi":"10.1080/2162402X.2026.2689769","DOIUrl":"10.1080/2162402X.2026.2689769","url":null,"abstract":"<p><p>Despite significant progress achieved by combining VEGFR tyrosine-kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICIs), complete responses remain rare in metastatic renal cell carcinoma (mRCC), highlighting the need for strategies that optimize therapeutic synergy. Here, we show that the efficacy of VEGFR blockade, vaccination, and PD-1 inhibition critically depends on treatment sequence. Using an orthotopic RENCA model, we show that short-term VEGFR inhibition with axitinib transiently remodels tumor vasculature, alleviates hypoxia, and limits suppressive myeloid subsets, thereby generating an immune-permissive window. Administering a survivin-based long-peptide vaccine (SVX) during this preconditioning phase elicits strong Th1-polarized CD4⁺ and cytotoxic CD8⁺ T-cell infiltration, which exhibit a polyfunctional cytokine and chemokine profile. When PD-1 blockade is introduced concomitantly with vaccination, after, rather than during, axitinib treatment, the triple regimen (axitinib + [SVX + anti-PD-1]) achieves durable tumor control with a high rate of complete responses, outperforming all other treatment schedules. Mechanistically, this sequence aligns vascular reprogramming, antigen-specific priming, and checkpoint release, converting an immune-excluded tumor into a T-cell-dominated, cytotoxic niche. Collectively, these findings identify temporal coordination as a critical determinant of therapeutic success and establish a mechanistically grounded framework for integrating vascular preconditionning, tumor-antigen vaccination, and PD-1 blockade as a curative immunotherapy strategy in renal carcinoma.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2689769"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320061","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":"Ex vivo-generated conventional dendritic cells type 1 and type 2 from blood progenitors induce potent antigen-specific T-cell immunity.","authors":"Jorge Cuenca-Escalona, Kevin Bos, Johanna Bödder, Tom van Oorschot, Tjitske Duiveman-de Boer, Georgina Flórez-Grau, I Jolanda M de Vries","doi":"10.1080/2162402X.2026.2695692","DOIUrl":"10.1080/2162402X.2026.2695692","url":null,"abstract":"<p><p>While existing cancer therapies manage to reduce tumor burden, they often fail to produce durable or curative outcomes. Alternatively, cell-based approaches - particularly dendritic cell (DC) vaccines conceal the potential to elicit robust tumor-specific T-cell responses, equipping patients with T-cells capable of eradicating tumor cells and preventing future relapses. To date, most DC vaccines have been generated with monocyte-derived DCs (moDCs), nowadays considered less potent at priming T-cells than blood-derived DC subsets, arguing for the usage of blood DCs for vaccine development. However, their scarcity in blood has hindered their clinical application, limiting their use in DC-based vaccination trials. To overcome this limitation, we developed a protocol to generate clinically relevant quantities of conventional DC type 1 (cDC1s) and DC2-like cells (cDC2s) from progenitor cells isolated from peripheral blood without the need for G-CSF mobilization, enabling their use for autologous vaccinations. The protocol is feeder layer free, yields clinically relevant amounts of cDC1s and cDC2s-like cells, and can be translated into a GMP-compliant setup. The ex vivo-generated DCs resemble their natural counterparts, acquire a robust pro-inflammatory phenotype (e.g., CD83, CCR7, and IL-12p70), and efficiently expand pro-inflammatory T-cells (e.g., IFN-<i>γ</i>). Notably, in an in vitro immunization model, these DCs primed naive T-cells for the expansion of tumor-antigen-specific CD8 T-cells exhibiting strong immune-stimulating features (e.g., IFN-<i>γ</i>, CD107a). In summary, this study demonstrates that blood progenitors differentiate into cDC1 and cDC2-like cells capable of eliciting potent antigen-specific T-cell subsets, offering a promising avenue for the development of more effective DC-based cancer therapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2695692"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148363311","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}