Oncoimmunology最新文献

{"title":"Early local immune activation following intra-operative radiotherapy in human breast tissue.","authors":"Anna Tiefenthaller, Nikko Brix, Roman Hennel, Montserrat Pazos, Bernd Kost, Vera von Bodungen, Brigitte Rack, Rachel Wuerstlein, Benjamin Frey, Udo S Gaipl, Julia Hess, Kristian Unger, Benedek Dankó, Martin Selmansberger, Horst Zitzelsberger, Nadia Harbeck, Claus Belka, Heike Scheithauer, Kirsten Lauber","doi":"10.1080/2162402X.2026.2653318","DOIUrl":"10.1080/2162402X.2026.2653318","url":null,"abstract":"<p><p>The local immune effects of cancer radiotherapy remain poorly characterized in humans due to limited access to irradiated tissue. Mechanistic insights largely derive from preclinical models employing tumor-intact, neoadjuvant-like settings. Here, we present real-world immunoprofiling data from breast cancer patients undergoing breast-conserving surgery with (<i>n</i> = 20) or without (<i>n</i> = 29) intraoperative radiotherapy (IORT). Postoperative wound fluid samples were analyzed by flow cytometry, multiplex cytokine profiling, and bulk RNA-sequencing, alongside systemic immune monitoring in peripheral blood. IORT triggered rapid local accumulation of distinct innate immune cell subsets and cytokines mediating recruitment, activation, and innate-adaptive crosstalk, accompanied by systemic features consistent with emergency hematopoiesis. Transcriptomic profiling of wound fluid mononuclear cells revealed enrichment of proinflammatory IL-6-JAK/STAT3 signaling. <i>In vitro,</i> irradiation of primary breast tissue cells recapitulated key cytokine patterns and led to robust senescence induction, suggesting irradiated, senescent normal tissue cells as drivers of early immune activation in postsurgical radiotherapy. These data provide direct clinical evidence that radiotherapy shapes local and systemic immune responses, offering mechanistic insights with clear relevance for tumor immunology and the development of rational radiotherapy‒immunotherapy combination strategies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2653318"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628947","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":"A mixed inflammatory peripheral signature defines clinical outcomes in a phase II trial combining pembrolizumab with paclitaxel and carboplatin in melanoma.","authors":"Caroline Lambert, Rahima Jamal, Paméla Thébault, Eftihia Cocolakis, Karl Bélanger, Jeanne Dionne, Jean-François Cailhier, Huy Le, Caroline Letendre, Stéphanie Lepage, Yelena Shechtman, Réjean Lapointe, Wilson H Miller","doi":"10.1080/2162402X.2026.2631244","DOIUrl":"10.1080/2162402X.2026.2631244","url":null,"abstract":"<p><p>Checkpoint blockade of PD-1 with pembrolizumab provides long-term survival to a significant proportion of patients with metastatic melanoma. Pembrolizumab has been successfully used in combination with chemotherapy in non-small-cell lung cancer to increase the response rate. This phase II trial combined pembrolizumab with carboplatin/paclitaxel (CP) to assess its safety and efficacy, and to identify correlates of responses. Thirty patients without prior immunotherapy for unresectable/metastatic melanoma were treated with pembrolizumab and CP. Peripheral blood was collected at baseline and after 2 cycles to characterize systemic immune activity by multiplex assays and flow cytometry. Seventy percent of patients received all 4 cycles of CP; 87% received pembrolizumab for 2 y or until progression. Grade 3 and higher adverse events (AEs) occurred in 50% of the patients. The overall response rate (ORR) and disease control rate (DCR) by irRC criteria were 43% and 53%, respectively. Median overall survival (OS) was 23.8 months. Objective response was associated with a lower frequency of naive CD8 T cells and low plasma CCL3 at baseline, along with a larger proportion of mature NK cells and of CD4 T cells expressing BTLA or LAIR-1. Survival rate was higher for patients with lower baseline of IL-6, IL-8, and CD4⁺CD39⁺ T cells. Following treatment, pro-inflammatory soluble factors increased in both responders and non-responders. Addition of CP to pembrolizumab in this study did not appear to result in a response or survival advantage and was less tolerable than immunotherapy alone. Correlative data point to peripheral signals to investigate further as potential biomarkers. Trial registration: clinicaltrials.gov, NCT02617849, registered on December 1st, 2015.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2631244"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12934184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277279","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":"Immunogenicity of neoantigens from hepatocellular carcinoma patients treated with a combined radioimmunotherapy.","authors":"Belén Aparicio, Leyre Silva, Marta Ruiz, Diana Llópiz, David Repáraz, Patrick Theunissen, Ibon Tamayo, Josune Egea, Ana Igea, Cristian Smerdou, Maria Peñas, Cristina Perpiñá, Ana Matilla, María Varela, Maria Reig, Manuel de la Torre-Alaez, Josepmaria Argemí, Bruno Sangro, Sandra Hervás-Stubbs, Pablo Sarobe","doi":"10.1080/2162402X.2026.2645280","DOIUrl":"10.1080/2162402X.2026.2645280","url":null,"abstract":"<p><p>In some cancers, patients responding to immune checkpoint inhibitors (ICI) usually harbor tumors with a higher tumor mutational burden and increased lymphocyte infiltration targeting mutation-derived neoantigens (neoAgs). In the NASIR-HCC trial, patients with hepatocellular carcinoma (HCC) received selective internal radiation therapy and the anti-PD-1 antibody Nivolumab, but many of them did not achieve clinical benefit (B). Since neoAg-based vaccination could enhance tumor infiltration and ICI responses, we studied neoAg-specific immunity in these patients and assessed whether patients with no benefit (NB) harbored sufficient immunogenic neoAgs for therapeutic vaccination. Using predicted neoAgs from 6 B and 4 NB patients, we tested immune reactivity <i>in vitro</i>. NeoAg-specific responses were detected in 75% of B and 83% of NB patients, recognizing 37% and 63% of neoAgs tested, respectively. <i>In vivo</i> immunization experiments in HLA transgenic HHD-DR1 mice using HLA-A*02.01- or HLA-DRB1*01-predicted neoAgs from four NB patients revealed responses against most neoAgs (87% and 73%, respectively), expanding the repertoire of immunogenic epitopes. Finally, polyepitopic peptide vaccination containing neoAgs from an NB patient induced stronger and broader T-cell responses compared to polyepitopic DNA vaccine. Our results demonstrate the immunogenicity of neoAgs in our cohort, supporting their potential utility in therapeutic vaccines designed to boost antitumor immunity.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2645280"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482157","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":"Polarization of tumor-infiltrating macrophages predicts complete response to neoadjuvant treatment in patients with rectal cancer.","authors":"Aylin Alkan, Fabian Byvald, Rode Grönkvist, Gustaf Danielsson, Joshua Cumming, Peter Falk, Eva Angenete, Ulf Yrlid","doi":"10.1080/2162402X.2026.2641261","DOIUrl":"10.1080/2162402X.2026.2641261","url":null,"abstract":"<p><p>Characterizing the composition of immune cells in the tumor microenvironment (TME) has shown promise in understanding variable responses to neoadjuvant treatment in rectal cancer. Despite this, no method has been established that can confidently predict the response to pre-operative chemoradiotherapy. Tumor-associated macrophages (TAMs) in the TME can be polarized by the biochemical milieu to adopt pro-inflammatory (M1-like) and anti-inflammatory (M2-like) phenotypes. Utilizing the spectrum of TAM polarization as a biomarker to predict patient response to neoadjuvant therapy in rectal cancer patients has not been fully explored. We address this using 7-plex immunofluorescence staining to quantify 16 subsets of TAMs in rectal adenocarcinoma pretreatment biopsies. Pretreatment biopsies were obtained from 128 patients with known tumor regression grades (TRG). Through quantifying the prevalence of TAM subsets, we identified a higher density of the completely M1-polarized subset and a lower density of the completely M2-polarized subset in patients with a complete pathological response, the absence of detectable tumor cells following treatment. Predictive modeling using TAM subsets showed that only the densities of two completely polarized subsets were predictors of therapeutic response in patients with rectal cancer. Significantly, we demonstrate that the full panel of markers we employed were required to define predictive populations, as total TAMs or TAM subsets defined by fewer markers were incapable of predicting treatment response. Taken together, we validate the utility of a multiplex approach to define the spectrum of TAM polarization, which can be leveraged to identify patients that will have a complete pathological response to neoadjuvant treatment.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2641261"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436966","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":"An orthotopic organoid-based model to study early CD8⁺ T cell dysfunction and immunotherapy response in colorectal cancer.","authors":"Lorenzo Lucantonio, Ludovica Schiano, Francesca Sozio, Andrea Kosta, Giovanna Peruzzi, Rosa Molfetta, Giuseppe Pietropaolo, Mattia Laffranchi, Antonio Francesco Campese, Giovanni Bernardini, Silvano Sozzani, Angela Gismondi, Angela Santoni, Giuseppe Sciumè, Stabile Helena, Cinzia Fionda","doi":"10.1080/2162402X.2026.2674362","DOIUrl":"10.1080/2162402X.2026.2674362","url":null,"abstract":"<p><p>Colorectal cancer (CRC) treatment represents a major clinical challenge, with immunotherapy providing durable responses only in a minority of patients. A deeper understanding of CD8⁺ T cell exhaustion and its contribution to immune checkpoint inhibitor (ICI) responsiveness is essential for the development of more effective therapeutic strategies. Preclinical models that faithfully reproduce the immune landscape of human CRC are therefore critical to address these challenges. Here, we established a syngeneic organoid-based orthotopic CRC mouse model by transplanting quadruple mutant <i>Apc</i>^{<i>⁻/⁻</i>}<i>Kras</i>^{<i>G12D/+</i>}<i>Trp53</i>^{<i>R172H/⁻</i>}<i>Smad4</i>^{<i>⁻/⁻</i>} (AKPS) intestinal organoids into the rectal submucosa of immunocompetent mice. Single-cell transcriptomic profiling revealed that CD8⁺ T cells represent the predominant leukocyte population within the tumor infiltrate and comprise populations transitioning toward dysfunction. Functionally, CD8⁺ T cell depletion led to increased tumor burden in orthotopic AKPS implants, underscoring their antitumor activity. Importantly, anti-PD-1 treatment increased the abundance of dysfunctional CD8⁺ T cell populations within AKPS tumors and reduced tumor growth, demonstrating the responsiveness of this model to ICIs. In contrast, subcutaneous implants of AKPS were infiltrated by mixed CD4⁺ and CD8⁺ T cell subsets, with CD8⁺ T cells exhibiting a markedly less dysfunctional profile, highlighting the limitations of heterotopic tumor models for studying antitumor immune responses. Together, our findings establish the AKPS orthotopic CRC model as a platform to dissect the molecular mechanisms of early CD8⁺ T cell dysfunction and to preclinically evaluate novel immunotherapeutic interventions in CRC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2674362"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147949939","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":"TNF-α deficiency underlies NK cell dysfunction in colorectal cancer.","authors":"Silvia Ruggeri, Beatrice Pizzitola, Mattia Laffranchi, Laura Beltrame, Giuseppe Sciumé, Alessio Grimaldi, Enrico Fiori, Roberto Caronna, Valerio De Peppo, Gian Luca Grazi, Valentina Laquintana, Giulia Turri, Silvano Sozzani, Angela Gismondi, Cinzia Fionda, Angela Santoni, Helena Stabile","doi":"10.1080/2162402X.2026.2636311","DOIUrl":"10.1080/2162402X.2026.2636311","url":null,"abstract":"<p><p>Natural killer (NK) cells are central to innate antitumor immunity, yet their function is systemically compromised in colorectal cancer (CRC). We show that CRC patients exhibit early and pronounced alterations in peripheral blood NK cells, marked by a reduced frequency of total CD56⁺ cells, a shift toward the CD56^lowCD16⁺ subset, and impaired cytotoxic and cytokine responses. Notably, plasma from CRC patients, particularly those with advanced disease, induces similar dysfunctions in healthy donor (HD) NK cells, suppressing mTORC1 signalling and effector activity. Transcriptomic profiling of HD NK cells exposed to CRC plasma revealed downregulation of TNF-<i>α</i> signalling components, concordant with reduced systemic and intracellular TNF-<i>α</i> levels in patients. Additionally, CRC plasma suppressed the JAK-STAT pathway and upregulated SOCS family genes, further dampening NK cell responsiveness. Inhibition of TNF-<i>α</i> in HD NK cells recapitulated the CRC plasma-induced defects, while exogenous TNF-<i>α</i> partially restored NK cell function, including STAT5 and S6 phosphorylation. These findings uncover TNF-<i>α</i> signalling deficiency as a systemic mechanism of NK cell suppression in CRC, linking impaired metabolism to immune evasion. Targeting this axis may offer a novel strategy to reinvigorate NK cell-mediated antitumor immunity in CRC.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2636311"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12940107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311655","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":"Modular mRNA cocktail enables synergistic activation of antigen-specific T cells for cancer immunotherapy.","authors":"Toan Van Le, Shota Imai, Iriya Fujitsuka, Makie Ueda, Sayuri Nakamae, Shusaku Mizukami, Rikinari Hanayama, Tomoyoshi Yamano","doi":"10.1080/2162402X.2026.2736339","DOIUrl":"10.1080/2162402X.2026.2736339","url":null,"abstract":"<p><p>mRNA-based therapeutics have demonstrated notable success in SARS-CoV-2 vaccines and are emerging in cancer immunotherapy. However, conventional mRNA cancer vaccines are limited in part by the low immunogenicity of tumor-associated and neoantigens. We addressed this limitation by formulating a modular, liposome-based mRNA cocktail comprising three distinct mRNAs encoding tumor antigens, the co-stimulatory molecule CD80, and membrane-tethered IL-2. Administration of this mRNA cocktail resulted in synergistic activation of tumor antigen-specific CD8⁺ T cells and robust anti-tumor immune responses. In addition, substituting IL-2 in the mRNA cocktail with membrane-tethered IL-12 led to the expansion and differentiation of endogenous antigen-specific Th1 helper T cells in vivo. Importantly, this platform activated NY-ESO-1-specific CD8⁺ T cells in HLA-A*02:01-transgenic mice, highlighting its translational potential. This modular mRNA cocktail provides a flexible and translatable platform for precision cancer immunotherapy by enabling coordinated activation of both CD8⁺ and CD4⁺ T cell responses.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2736339"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026478","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":"Purinergic activity of circulating extracellular vesicles associates with disease progression in melanoma.","authors":"Yana G Najjar, Chang Sook Hong, Elizabeth V Menshikova, John M Kirkwood, Brenda Diergaarde, Edwin K Jackson, Theresa L Whiteside","doi":"10.1080/2162402X.2026.2688603","DOIUrl":"10.1080/2162402X.2026.2688603","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) produced by melanoma cells (MTEX) carry ecto-nucleotidases, CD39/CD73, on their surface membrane, produce adenosine (ADO), and deliver it to immune recipient cells, inducing immune suppression. Based on studies of MTEX from melanoma cell lines, we hypothesized that MTEX are the major producers of ADO in cancer patients' plasma, which contains a variable mix of MTEX and NTEX. To test this hypothesis, EVs were isolated from the plasma of melanoma patients with no evidence of disease (NED) or with metastatic disease at phlebotomy, and MTEX were separated from EVs produced by non-malignant cells (NTEX) by immune capture using anti-CSPG4 mAbs. The purinergic activity of CD39/CD73 in total plasma EVs and NTEX was measured by high-pressure liquid chromatography with fluorescence detection, and that in MTEX was calculated. Unexpectedly, NTEX showed higher levels of purinergic activity than MTEX. While higher purinergic activity of NTEX <i>vs.</i> MTEX was not associated with disease status, the CD73 activity in total EVs was correlated with disease progression: it was significantly higher in patients with metastatic disease compared to those with NED (<i>P</i> = 0.02). Our data suggest that in the plasma of cancer patients, both MTEX and NTEX contribute to the purinergic metabolism mediated by EVs. Thus, the total EV fraction in plasma of melanoma patients provides a clinically meaningful assessment of purinergic activity and potentially can serve as a personalized estimate of levels of ADO-driven immune suppression in patients.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2688603"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148297139","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":"Killing cancer takes guts: lessons learned from the manipulation of gut microbiome and immunotherapy for the future of urothelial carcinoma.","authors":"Nihaal Reddy, Kire Lau, Jacob Naman, Kevin Lu, Erin McGillivary, Amirali Salmasi, Michael Liss, Tyler Stewart","doi":"10.1080/2162402X.2025.2611458","DOIUrl":"10.1080/2162402X.2025.2611458","url":null,"abstract":"<p><p>Urothelial carcinoma (UC) remains a common cancer with significant morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have helped revolutionize the treatment of UC, and there is growing evidence suggesting the crucial role of the gut microbiome in immune system function influences immunotherapy outcomes in this disease. Herein, we review the preclinical basis for how manipulation of the gut microbiome may alter the efficacy of immunotherapy for patients with cancer, highlight interventions optimizing gut microbiome diversity currently in use, review recent and ongoing clinical trials supporting the role of the gut microbiome in improving immunotherapy outcomes, and discuss clinical implications to improve outcomes for UC patients with immunotherapy in the real world. There is growing evidence that suggests that specific gut microbiome compositions significantly modulate the host immune system and response to ICIs. Early studies have shown that certain microbial taxa enhance antitumor immunity by influencing T cell priming, dendritic cell activation, and cytokine production. Fecal microbiota transplantation (FMT), probiotic supplementation, and dietary modulation have emerged as promising methods to alter microbiomes to improve immunotherapy outcomes. Taxa from positive immunotherapy responders across a variety of cancers demonstrate beneficial effects when transplanted into both treatment-naive or prior nonresponders. Increasing evidence suggests that the gut microbiome plays a crucial role in cancer care, particularly when patients are treated with immunotherapy. Future studies are needed to better understand the underlying mechanisms. While some studies are currently underway to explore gut manipulation for patients with UC, more studies are needed to investigate the potential to convert nonresponders into responders through microbiome manipulation.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2611458"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012949","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":"PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma.","authors":"Luca Lippert, Ava Kleinwächter, Anna Ohradanova-Repic, Filip Horvat, Lisa-Marie Appel, Lena Walch, Niccolò Bragato, Jakob Wimmer, Hanna Wopfner, Anna Röhrer, Magdalena Engl, Kapil Upadhyaya, Joachim Widder, Michael S Cohen, Dea Slade","doi":"10.1080/2162402X.2026.2656053","DOIUrl":"10.1080/2162402X.2026.2656053","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most lethal form of brain cancer with an immunosuppressive tumor microenvironment (TME). Radio- and chemotherapy can modify the TME and elicit anti-tumor immunity through the STING and type I interferon (IFN-I) pathways. STING agonists or DNA damage response inhibitors can potentiate the effects of radiation by targeting the IFN-I pathway. Here, we examined the immunogenic response of GBM cells to hypofractionated or single-dose radiation combined with a STING agonist or inhibitors targeting immune signaling (PARP7), the DNA damage response, cell cycle checkpoints or autophagy. We found that hypofractionated radiation elicited a ferroptosis-dependent IFN-I response and that the PARP7 inhibitor KMR-206 and the STING agonist diABZI enhanced the effects of radiation by activating immune cells. In patient-derived GBM cancer stem cells with low STING levels, the PARP7 inhibitor was more effective at inducing immunogenic signaling compared to the STING agonist. Our results highlight the potential of PARP7 inhibitors as a new treatment to boost anti-tumor immunity in GBM, which may be more advantageous compared to STING agonists given that STING is often downregulated in GBM.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"15 1","pages":"2656053"},"PeriodicalIF":6.2,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677959","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}