Oncoimmunology最新文献

{"title":"Dectin-1 signaling promotes Galectin-3 shedding and expansion of immunosuppressive CD71+ erythroid cells in breast cancer.","authors":"Ako Azimi, Amirhossein Rahmati, Shima Shahbaz, Zahra Elahi, Alireza Zahiriabyaneh, Junyan Cao, Ernesto Luisito Padua, Chloe Church, Emmanuel T Alimo, Afsaneh Lavasanifar, John Walker, Shokrollah Elahi","doi":"10.1080/2162402X.2026.2682649","DOIUrl":"10.1080/2162402X.2026.2682649","url":null,"abstract":"<p><p>Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment, yet many patients fail to respond, underscoring the need to better understand mechanisms of resistance. One emerging mechanism involves the recruitment of erythroid progenitors and precursors, known as CD71+ erythroid cells (CECs), to the tumor microenvironment. Using murine models of triple-negative breast cancer (TNBC), we investigated the therapeutic effects of curdlan, a <i>β</i>-glucan. We found that TNBC was associated with extramedullary erythropoiesis and expansion of CECs. Unexpectedly, curdlan worsened tumor progression by further increasing CEC abundance. Immunophenotypic analysis revealed a marked expansion of Galectin-3 (Gal-3)+ CECs in both spleen and tumor. Mechanistically, our findings suggest that curdlan-Dectin-1ligation induces Gal-3 shedding from CD11b+cells, enabling its deposition onto CECs. Notably, we discovered that Gal-3 is co-expressed and colocalized with PD-L1 and Dectin-1 on CECs. Importantly, PD-L1 blockade substantially reduced immunosuppressive Gal-3+PD-L1+ CECs, suppressed extramedullary erythropoiesis, and induced pronounced tumor regression. Re-analysis of publicly available scRNAseq datasets further confirmed the abundance of Gal-3+ CECs in human bone marrow. Collectively, these findings identify Gal-3+PD-L1+ CECs as key drivers of an immunosuppressive tumor microenvironment and reveal a previously unrecognized axis through which PD-L1 blockade exerts therapeutic benefit in breast cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2682649"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13232887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145243","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":"Comparison of epcoritamab, lenalidomide, and rituximab versus usual care in relapsed/refractory follicular lymphoma.","authors":"Lorenzo Falchi, Martin Hutchings, David Tybor, Junhua Yu, Abualbishr Alshreef, Anthony Wang, Kavita Sail, Zhijie Ding, Alex Mutebi, Poliana Patah, Nisha Kishore, Ali Rana, Elena Favaro, Kim Linton","doi":"10.1080/2162402X.2026.2691549","DOIUrl":"10.1080/2162402X.2026.2691549","url":null,"abstract":"<p><p>Patients with relapsed/refractory follicular lymphoma (R/R FL) often experience multiple disease recurrences with progressively shorter duration of remission. Chemoimmunotherapy (CIT) is commonly used for R/R FL in second-line and later settings but is not curative; novel, improved treatments are needed. Epcoritamab, a CD3 × CD20 bispecific antibody, is approved as monotherapy for R/R FL after ≥ 2 lines of therapy (LOTs) and combined with lenalidomide and rituximab (R²) for R/R FL. Epcoritamab + R² pivotal data demonstrated superiority over R², but no comparison of epcoritamab + R² versus CIT exists. Therefore, we conducted an adjusted comparative analysis of epcoritamab + R² from arm 2 of the phase 1b/2 EPCORE NHL-2 trial (NCT04663347; <i>n</i> = 111; US, 23.4%) versus R²/CIT using COTA individual patient-level electronic health records (<i>n</i> = 380; US, 100%) of patients with R/R FL after ≥ 1 previous LOT. Epcoritamab + R² improved response rates over R²/CIT (overall response, 96.9% versus 80.5%, <i>P</i> < .001; complete response, 90.2% versus 55.1%, <i>P</i> < .001). Epcoritamab + R² improved duration of response (HR, 0.29 [95% CI, 0.18-0.47]; <i>P</i> < .001), duration of complete response (HR, 0.31 [95% CI, 0.17-0.55]; <i>P</i> < .001), progression-free survival (HR, 0.43 [95% CI, 0.28-0.68]; <i>P</i> < .001), and overall survival (HR, 0.33 [95% CI, 0.16-0.70]; <i>P</i> = .003) over R²/CIT. These findings support epcoritamab + R² as a promising chemotherapy-free treatment option for R/R FL.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2691549"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13349012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406661","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":"Pharmacological inhibition of MAPK P38α rescues the immune defect of dendritic cells affected by the FPR1 loss-of-function polymorphism rs867228.","authors":"Liwei Zhao, Oliver Kepp, Peng Liu, Guido Kroemer","doi":"10.1080/2162402X.2026.2652088","DOIUrl":"https://doi.org/10.1080/2162402X.2026.2652088","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2652088"},"PeriodicalIF":6.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628925","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":"Pleiotropic effects of BET inhibition broadly boost tumor immunogenicity to CD8^<b>+</b> T cells.","authors":"Jeroen Melief, Lucas Baldran-Groves, Marc-Antoine Gerault, Ying Yu Liang, Sylvya Pasca, Mireia Cruz de Los Santos, Stina Wickström, Tanja Lövgren, Anderson Daniel Ramos, Lars-Gunnar Larsson, Pär Nordlund, Barbara Seliger, Rolf Kiessling","doi":"10.1080/2162402X.2026.2658916","DOIUrl":"10.1080/2162402X.2026.2658916","url":null,"abstract":"<p><p>BET inhibitors (BETi) have shown potential to augment tumor immunogenicity in melanoma. However, conflicting evidence exists regarding their precise mechanism of action, and their overall impact on melanoma immunogenicity and antitumoral T cell responses remains unclear. To address this, human melanoma cell lines treated with JQ1 and/or IFNγ were investigated for gene and protein expression changes in key pathways governing immunogenicity and cocultured with autologous tumor-infiltrating lymphocytes (TIL) with known antigen-specificity. JQ1-induced proteome-wide alterations were examined using mass spectrometry-based cellular thermal shift assay (MS-CETSA), which revealed that JQ1 broadly impacts melanoma immunogenicity by regulating IFN signaling, antigen processing and presentation, and innate immune signaling pathways. More specifically, JQ1 enhanced JAK1/STAT1 signaling and upregulated components of the HLA class I (HLA-I) antigen processing and presentation machinery (APM), increased MART-1 expression while concomitantly dampening tumoral expression of PD-L1, IDO1, and HLA class II (HLA-II). Functionally, JQ1 markedly improved tumor recognition by autologous MART-1- and neoantigen-specific CD8⁺ TIL, while dampening CD4⁺ TIL activation through the downregulation of Cathepsin S (CTSS). Preliminary results using JQ1-treated melanoma cells in a mixed lymphocyte-tumor cell culture (MLTC) markedly enhanced TIL proliferation and resulted in a T cell product enriched for CD8⁺ T cells. These findings reveal how the pleiotropic effects of BETi on melanoma cells broadly boost their immunogenicity towards CD8⁺ T cells and uncover novel pathways that might be therapeutically exploited to enhance CD8⁺ T cell-mediated anti-tumor immunity in <i>ex vivo</i> and <i>in vivo</i> approaches to cancer immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2658916"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786354","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":"Single-cell sequencing profiling of intratumoral heterogeneity and immunosuppressive microenvironment in primary thyroid cancer and lymph node metastases.","authors":"Shuhang Xu, Yaorong Su, Senmin Zhang, Dongye Huang, Song Wu, Cailu Song, Wenhuan Zhong, Lan Xie, Wenkuan Chen","doi":"10.1080/2162402X.2026.2701504","DOIUrl":"10.1080/2162402X.2026.2701504","url":null,"abstract":"<p><p>Metastasis is a major determinant of treatment failure and mortality in thyroid cancer, yet the interplay between malignant evolution and the immune microenvironment remains poorly characterized. Immunotherapy offers promise, but its efficacy requires a deeper understanding of tumor-associated immune infiltration and checkpoint regulation. In this study, we constructed a high-resolution transcriptomic atlas of the thyroid cancer ecosystem by analyzing 55,005 single cells from paired primary tumors and lymph node metastases. By integrating chromosomal copy number variation (CNV) inference with consensus nonnegative matrix factorization (cNMF), we deciphered the intrinsic heterogeneity of malignant epithelial cells, revealing distinct transcriptional programs and developmental trajectories driving the metastatic cascade. The metastatic niche exhibited significant reprogramming of the immunosuppressive landscape, characterized by the enrichment of FOXP3⁺ regulatory T (Treg) cells, LAMP3⁺ dendritic cells (DCs), and CCL18⁺ M2-like macrophages. Notably, while canonical checkpoints PD-1 and PD-L1/2 showed minimal expression, ligand-receptor interaction analysis identified the LAG3-LGALS3 axes as dominant immune evasion pathways mediating the crosstalk between CD8⁺ T cells and the tumor stroma. In conclusion, this study comprehensively maps the coevolution of malignant thyrocyte plasticity and the immunosuppressive metastatic niche. By uncovering the specific role of LAMP3⁺ DCs and identifying LAG3/TIGIT as critical alternative checkpoints, our findings challenge the utility of conventional PD-1 blockade in this context and provide a robust molecular rationale for developing next-generation immunotherapeutic strategies tailored to thyroid cancer. Although limited by a modest sample size, these findings provide a foundation for further investigation of the metastatic immune landscape in thyroid cancer.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2701504"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13360498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425772","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":"Early neutrophil infiltration promotes TRIMELVax-induced antitumor immunity by linking local inflammation to tumor control.","authors":"Amarilis Pérez-Baños, María Alejandra Gleisner, Andrés Tittarelli, Daniela Tapia, María Elisa Cuevas, Antonia Mardonez, Fabián Tempio, Rosario Astaburuaga-García, Iván Flores, Cristian Pereda, Álvaro Lladser, Fermín E González, Sebastián Valenzuela, Micaela Ricca, María Inés Becker, Nils Blüthgen, Adnane Achour, Flavio Salazar-Onfray","doi":"10.1080/2162402X.2026.2680766","DOIUrl":"10.1080/2162402X.2026.2680766","url":null,"abstract":"<p><p>Enhancing innate-adaptive immune crosstalk is key for improving cancer vaccine efficacy. TRIMELVax is a heat shock-conditioned whole-tumor-cell vaccine combining xenogeneic melanoma cell lysate, syngeneic B16F10 melanoma cell lysate, and <i>Concholepas concholepas</i> hemocyanin. Although TRIMELVax elicits robust antitumor responses in preclinical models, the mechanisms underlying its efficacy remain poorly defined. We characterized the early immune events triggered by TRIMELVax in mice using RT-qPCR, high-dimensional flow cytometry, immunohistochemistry, CFSE-based dendritic cell (DC) migration assays, and therapeutic melanoma models with transient neutrophil depletion. TRIMELVax elicited a rapid inflammatory response at the vaccination site, characterized by local upregulation of <i>CXCL3, CXCL5, CXCL9, CCL3, CCL4, CCL12, IL-1β, IL-6/OSM, IL-12a</i>, and <i>G-CSF</i>. This response drove an early influx of neutrophils and monocytes, followed by increased accumulation of cDC1, cDC2, and monocyte-derived DCs. Notably, we identified a transient population of neutrophils expressing markers associated with antigen-presenting cells (CD45⁺, CD11b⁺, Ly6G⁺, CD11c⁺, MHC-II⁺) that emerged within 12-24 hours postvaccination. These APC-like neutrophils colocalized with cDC1 at the injection site and subsequently migrated to the popliteal draining lymph nodes (pLN). Neutrophil depletion impaired cDC1 migration, reduced APC accumulation in pLN, and abolished the therapeutic efficacy of TRIMELVax. Together, these findings identify neutrophils as key early regulators of the innate inflammatory environment induced by TRIMELVax and suggest that neutrophils with APC-like features may impact DC trafficking and downstream antitumor immunity. Neutrophils, particularly those with APC-like phenotypes, emerge as promising cellular adjuvant targets for enhancing cancer vaccination strategies, offering a new avenue for rational vaccine design and combination with checkpoint blockade therapies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2680766"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148319981","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":"Preclinical evaluation of homodimeric FAPI target modules for UniCAR-mediated targeting of FAP-expressing tumor and stromal cells.","authors":"Hugo Boutier, Simona Mattiussi, Liliana R Loureiro, Nicole Berndt, Antonia Stammberger, Nathalia Jones-Cifuentes, Lydia Hoffmann, Emile Verhulst, Marc Schmitz, Ingrid De Meester, Umberto M Battisti, Claudia Arndt, Anja Feldmann, Frank Roesch, Matthias M Herth, Michael Bachmann","doi":"10.1080/2162402X.2026.2717836","DOIUrl":"10.1080/2162402X.2026.2717836","url":null,"abstract":"<p><p>Due to its overexpression in the tumor microenvironment of most solid malignancies, fibroblast activation protein (FAP) has emerged as an ideal target for (immuno)theranostic applications. The clinically tested UniCAR system represents a promising adapter CAR T-cell approach, in which CAR T-cell activity is regulated through the administration of target modules (TMs). Here, we report the first homodimeric FAP inhibitor (FAPI)-based TMs that enable efficient adapter CAR T-cell immunotherapy of FAP-positive tumors. The novel TMs consist of two UAMC-1110 FAPI moieties, the E5B9 UniCAR epitope, a suitable polyethylene glycol spacer to ensure epitope accessibility, and a functional group that allows for further TM functionalization for diagnostic and radiotherapeutic applications. Following the synthesis of the novel FAPI TMs, we evaluated their functionality using both in vitro and in vivo models. The FAPI TMs successfully redirect UniCAR T-cells and mediate potent lysis of FAP-positive cells in vitro and in an immunodeficient mouse model. In addition, we established a 3D heterospheroid model consisting of tumor cells expressing prostate stem cell antigen (PSCA) alongside FAP-positive stromal fibroblasts. We showed that simultaneous dual-targeting leads to enhanced UniCAR-mediated cytotoxicity. Notably, fibroblast killing is mediated by the release of PSCA from dying tumor cells and its subsequent binding to the surface of neighboring PSCA-negative fibroblasts, thereby making them susceptible to PSCA-directed targeting. Overall, our work not only summarizes the successful development of novel dimeric FAPI adapter molecules for immunotherapeutic applications in solid tumors but also provides novel insights into the targeting of PSCA-positive tumors.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2717836"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799945","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":"STAT3 inhibition for the induction of immunogenic cell death in multiple myeloma.","authors":"Oliver Kepp, Guido Kroemer","doi":"10.1080/2162402X.2026.2732727","DOIUrl":"10.1080/2162402X.2026.2732727","url":null,"abstract":"<p><p>In a recent paper published in <i>Blood Science</i>, Sha et al. report that STAT3 inhibition eliminates multiple myeloma stem-like cells while eliciting hallmarks of immunogenic cell death. These highly intriguing findings connect stemness, integrated stress response, and antitumor immunity, yet in vivo validation remains necessary before this strategy can be considered immunogenic.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2732727"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971919","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":"X‑ray FLASH RT inhibits lung cancer bone metastasis via activating CD4⁺ T-cell‑mediated antitumor immunity with modulation of Th17 cell response.","authors":"Yao Huang, Tao Wu, Wen Yang, Yuan-Yuan Liang, Yun-Fei Sun, Chao-Fan Ma, Ruo Tang, Rui-Ci Liang, Xue-Ting Zheng, Hui-Wen Luo, Cheng-He Ding, Xiao-An Li, Yan Zhou","doi":"10.1080/2162402X.2026.2706271","DOIUrl":"10.1080/2162402X.2026.2706271","url":null,"abstract":"<p><p>Lung cancer is characterized by rapid progression and poor prognosis, with 50%-70% of patients presenting local or distant metastasis at diagnosis, among which bone metastasis is the most common type. Radiotherapy is the standard approach for managing cancerous bone metastasis pain. Here, we report the first application of X-ray FLASH radiotherapy (RT) in treating lung cancer bone metastasis in mice. Using an intratibial LLC-luc cell injection model, mice were treated with FLASH RT (94 Gy/s) or conventional RT (CONV RT, 0.1 Gy/s) via a petal accelerator developed by the Institute of Fluid Physics, China Academy of Engineering Physics. The results demonstrated that X-ray FLASH RT and CONV RT exhibited comparable efficacy in suppressing tumor growth, and both may alleviate osteolytic lesions in mice with lung cancer bone metastasis through CD4⁺ T cell-dependent antitumor responses. However, FLASH RT further attenuated bone destruction by inhibiting osteoclastogenesis, remodeling the bone-tumor microenvironment, and reducing tumor invasion, with lower systemic toxicity. Notably, unlike CONV RT, FLASH RT instigates a distinct DNA damage response that drives oxygen depletion, thereby attenuating ROS accumulation. This mechanistic cascade sequentially suppresses cGAS-STING-NF-κB axis activation and dampens the ensuing inflammatory response. In addition, we observed a reduction in Th17 cell differentiation following FLASH RT compared to CONV RT, which may contribute to the differential efficacy of these two radiation modalities in attenuating lung cancer bone metastasis. Collectively, X-ray FLASH RT provides a promising therapeutic strategy for patients with bone metastases.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2706271"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992133","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":"NK cell-mediated tumor cell killing by bispecific innate cell engagers induces ADCC-mediated activation of primary human dendritic cells.","authors":"Lukas Heger, Tomasz Kaszubowski, Lukas Amon, Christian H K Lehmann, Susanne Wingert, José Medina-Echeverz, Joachim Koch, Holger Hackstein, Ariawan Purbojo, Arndt Hartmann, Christoph Alexiou, Robert Cesnjevar, Jens Pahl, Diana Dudziak","doi":"10.1080/2162402X.2026.2613561","DOIUrl":"10.1080/2162402X.2026.2613561","url":null,"abstract":"<p><p>Bispecific antibodies are used for the treatment of hematological malignancies as well as solid tumors. One of their main effector mechanisms is the recruitment of effector cells such as CD8⁺ T cells and CD16A⁺ NK cells to tumor cells. Bispecific innate cell engagers (ICE®) harnessing CD16A⁺ NK cells have been shown to induce significant tumor cell lysis in preclinical models, translating to promising signs of clinical activity together with a well-managed safety profile. However, how killing of tumor cells by NK cells influences other innate immune cells in the tumor microenvironment, such as dendritic cells (DCs), instrumental in bridging innate and adaptive tumor immunity, is largely unknown. Thus, we here analyzed whether antibody-dependent cell-mediated cytotoxicity by NK cells affected human DC subpopulations. We could show that killing of tumor cells leads to a strong activation of human conventional DCs type 1 (cDC1), DC2, and DC3 with enhanced expression of co-stimulatory molecules as well as the secretion of proinflammatory cytokines. Further, DC subpopulations as well as surviving tumor cells showed increased expression of the immunoregulatory molecule PD-L1 that is known to dampen T-cell immunity. Nevertheless, ADCC boosted the capacity of cDC1 and DC2 to prime naïve T cell responses but not of DC3. Thus, our data suggests that the therapy with bispecific antibodies targeting NK cells may have the potential to facilitate adaptive antitumor immune responses via activation of cDC1 and DC2.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2613561"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12818816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999482","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}