Oncoimmunology最新文献

{"title":"Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models.","authors":"Kimberly Pojar, Diana Reckendorfer, Judith Strauss, Sarah Szaffich, Sarah Ahmadi-Erber, Timo Schippers, Pedro Berraondo, Klaus K Orlinger, Josipa Raguz, Henning Lauterbach","doi":"10.1080/2162402X.2025.2514040","DOIUrl":"10.1080/2162402X.2025.2514040","url":null,"abstract":"<p><p>Among the plethora of cancer immune evasion mechanisms, T-cell-inhibiting factors within the tumor microenvironment impose a major challenge for the development of novel immunotherapies. Strategies to overcome immunosuppression and remodel the TME are therefore urgently needed. Therapeutic cancer vaccines based on engineered arenaviruses have been proven to generate potent tumor specific CD8+ T-cell responses in preclinical models and cancer patients. Despite signs of clinical activity as monotherapy, combination therapies are needed to further increase the therapeutic effect. To address this need, we evaluated the efficacy of recombinant vectors based on lymphocytic choriomeningitis virus encoding the T-cell stimulating cytokines IL-7, IL-12 and IL-15 with or without tumor-associated antigens. These vectors were tested in three different mouse tumor models (TC-1, MC-38 and B16.F10). Our results demonstrate that only IL-12 encoding vectors led to increased immunogenicity and efficacy, which, after systemic administration, was associated with adverse events. The safest and most potent regimen consisted of systemic vaccination with tumor antigen encoding vectors and local injection of IL-12-encoding vectors. A single round of this treatment regimen resulted in 86-100% tumor-free mice and warrants further investigation.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2514040"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259164","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":"Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death.","authors":"Karla Alvarez-Valadez, Jonathan G Pol, Guido Kroemer, Mojgan Djavaheri-Mergny","doi":"10.1080/2162402X.2025.2531113","DOIUrl":"10.1080/2162402X.2025.2531113","url":null,"abstract":"<p><p>Sertraline and indatraline are two antidepressants that function as serotonin reuptake inhibitors and have demonstrated promising anticancer potential, although their precise mechanisms of action remain unclear. Both compounds trigger cholesterol accumulation within lysosomes followed by lysosomal membrane permeabilization, ultimately leading to the activation of immunogenic cell death (ICD). This, in turn, triggers a T cell-mediated adaptive immune response that facilitates significant tumor control.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2531113"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602019","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":"TIGIT blockade in the context of BCMA-CART cell therapy does not augment efficacy in a multiple myeloma mouse model.","authors":"Aina Oliver-Caldes, Joan Mañe Pujol, Anthony M Battram, Lorena Perez-Amill, Mireia Bachiller, Hugo Calderon, Maria Castella, Judit Carpio, Sergi V Salsench, Natalia Tovar, Oriol Cardus, Alvaro Urbano-Ispizua, David F Moreno, Luis Gerardo Rodríguez-Lobato, Ester Lozano, Laura Rosiñol, Manel Juan, Beatriz Martín-Antonio, Carlos Fernández de Larrea","doi":"10.1080/2162402X.2025.2529632","DOIUrl":"10.1080/2162402X.2025.2529632","url":null,"abstract":"<p><p>BCMA-directed CAR-T therapies have shown promising results in multiple myeloma (MM). However, patients continue to relapse. T cell exhaustion with increased TIGIT expression is a resistance mechanism which was confirmed in CAR-T cells from ARI0002h trial, an academic CAR-T developed in our institution. We aimed to analyze the impact of blocking TIGIT on the efficacy of ARI0002h. We used three different strategies to block TIGIT: <i>(1)</i> Addition of an external blocking anti-TIGIT-antibody (Ab), <i>(2)</i> Modify ARI0002h into a 4^th generation CAR-T, named ARITIGIT, capable of secreting a soluble TIGIT-blocking scFv and <i>(3)</i> TIGIT knock-out in ARI0002h using CRISPR/Cas9. Each strategy was evaluated <i>in vitro</i> and <i>in vivo</i>. Adding a TIGIT-blocking Ab to ARI0002h improved <i>in vitro</i> cytotoxicity, but failed to enhance mice survival. The new 4^th generation CAR-T, ARITIGIT, was also unable to achieve better survival outcomes despite favoring the <i>in vivo</i> model by using a myeloma cell line with high expression of the TIGIT ligand PVR. Interestingly, when mice were challenged with a second infusion of tumor cells, mimicking a relapse model, a trend for improved survival with ARITIGIT was observed (<i>p</i> = 0.11). Finally, TIGIT-knock-out on ARI0002h (KO-ARI0002h) using CRISPR/Cas9 showed similar <i>in vitro</i> activity to ARI0002h. In an <i>in vivo</i> stress model, TIGIT KO-ARI0002h prolonged survival (<i>p</i> = 0.02). However, this improvement was not significant compared to ARI0002h (<i>p</i> = 0.07). This study failed to demonstrate a significant benefit of TIGIT-blockade on ARI0002h cells despite using three different approaches, suggesting that targeting a single immune checkpoint may be insufficient.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2529632"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620863","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":"Updates on radiotherapy-immunotherapy combinations: Proceedings of 8th Annual ImmunoRad Conference.","authors":"Fereshteh Talebi, Fabiana Gregucci, Jalal Ahmed, Nir Ben Chetrit, Brian D Brown, Timothy A Chan, Dhan Chand, Julie Constanzo, Sandra Demaria, Dmitry I Gabrilovich, Encouse Golden, Andrew Godkin, Chandan Guha, Gaorav P Gupta, Aisha Hasan, Fernanda G Herrera, Howard Kaufman, Donna Li, Alan A Melcher, Sierra McDonald, Taha Merghoub, Arta M Monjazeb, Sébastien Paris, Sean Pitroda, Anguraj Sadanandam, Dörthe Schaue, Laura Santambrogio, Phillippe Szapary, Julien Sage, James W Welsh, Anna Wilkins, Kristina H Young, Eric Wennerberg, Laurence Zitvogel, Lorenzo Galluzzi, Eric Deutsch, Silvia C Formenti","doi":"10.1080/2162402X.2025.2507856","DOIUrl":"10.1080/2162402X.2025.2507856","url":null,"abstract":"<p><p>The annual ImmunoRad Conference has established itself as a recurrent occasion to explore the possibility of combining radiation therapy (RT) and immunotherapy (IT) for clinical cancer management. Bringing together a number of preclinical and clinical leaders in the fields of radiation oncology, immuno-oncology and IT, this annual event fosters indeed essential conversations and fruitful exchanges on how to address existing challenges to expand the therapeutic value of RT-IT combinations. The 8th edition of the ImmunoRad Conference, which has been held in October 2024 at the Weill Cornell Medical College of New York City, highlighted exciting preclinical and clinical advances at the interface between RT and IT, setting the stage for extra progress toward extended benefits for patients with an increasing variety of tumor types. Here, we critically summarize the lines of investigation that have been discussed at the occasion of the 8th Annual ImmunoRad Conference.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2507856"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121204","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":"Systematic identification of lincRNA-derived immunogenic peptides in melanoma.","authors":"Emilie Dupré, Amélie Guiho, Tiffany Beauvais, Léna Labous, Tristan Cardon, Corine Bertolotto, Amir Khammari, Gaelle Quéreux, Michel Salzet, Nathalie Labarrière, Catherine Rabu, François Lang","doi":"10.1080/2162402X.2025.2538684","DOIUrl":"10.1080/2162402X.2025.2538684","url":null,"abstract":"<p><p>The search for reliable shared tumor-specific antigens (TSAs) to improve cancer immunotherapy is on-going. The so-called non-coding regions of the genome have recently been shown to give rise to immunogenic peptides, including the melanoma-specific antigen MELOE-1 which is translated from the long intergenic non-coding RNA (lincRNA) <i>meloe</i> in an IRES-dependent manner. Here, we present a strategy to systematically identify tumor-specific antigens produced by ORFs within lincRNAs with IRES-like upstream structures. We provide evidence suggesting that in the melanocytic lineage a significant proportion of the selected lincRNAs can produce immunogenic peptides. T cell repertoires against some of these peptides were found in peripheral blood mononuclear cells (PBMCs) from healthy donors and melanoma patients, and in tumor-infiltrating lymphocytes (TILs) from metastatic melanoma patients. Finally, CD8+ T cell lines from melanoma patients specific for three of the characterized HLA-A *0201 epitopes could recognize melanoma cell lines, which were enhanced by reticular stress. Thus, these peptides may represent a new class of shared TSAs in melanoma and are attractive candidates for evaluation as targets for immunotherapy in preclinical studies. In addition, our selection strategy has the potential to identify new lincRNA-derived antigens in other cancers.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2538684"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-infiltrating lymphocytes-derived CD8⁺ clonotypes infiltrate the tumor tissue and mediate tumor regression in glioblastoma.","authors":"Lucas C M Arruda, Julia Karbach, Dragan Kiselicki, Hans-Michael Altmannsberger, Evgueni Sinelnikov, Dirk Gustavus, Hans Hoffmeister, Akin Atmaca, Elke Jäger","doi":"10.1080/2162402X.2025.2559784","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2559784","url":null,"abstract":"<p><p>Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) has demonstrated consistent clinical efficacy in treating advanced melanoma and other \"hot\" tumors. However, it has shown limited success in \"cold\" tumors like glioblastoma. We present the successful treatment of a rapidly progressing glioblastoma patient with TILs expanded using a defined cytokine combination of IL-2, IL-15, and IL-21. The patient received lymphodepletion with cyclophosphamide one day pre-TIL infusion, followed by a single dose of IL-2 post-transfer. Complete tumor regression was observed after two TIL infusions administered two weeks apart. The TIL products were enriched for CD8⁺ T-cells and demonstrated specific lysis of the autologous tumor cell line. Transcriptomic analysis of tumor biopsies post-TIL infusion revealed increased expression of genes associated with immunological synapse formation and T-cell effector function, correlating with the patient's clinical outcome. T-cell receptor (TCR) next-generation sequencing of the infused TILs and post-treatment tumor biopsies confirmed the infiltration and expansion of TIL-derived clonotypes within the tumor microenvironment. CD8⁺ T-cell clonotypes exhibited robust tumor migration and expansion, while CD4⁺ T-cells showed limited tumor infiltration. In conclusion, TILs expanded with IL-2/IL-15/IL-21 represent a promising therapeutic approach for glioblastoma, overcoming traditional challenges posed by the tumor microenvironment and achieving significant clinical outcomes.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2559784"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239891","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":"NK92 cells stably transfected with CD16 are efficient against multiple myeloma cells <i>ex vivo</i> and <i>in vivo</i>, especially if combined with daratumumab.","authors":"David Giraldos, Evelyn Galano-Frutos, Laura Cambronero-Arregui, Manuel Beltrán Visiedo, Eduardo Romanos, Chantal Reina-Ortiz, Gemma Azaceta, Beatriz Martínez-Lázaro, Bárbara Menéndez-Jándula, Alejandro García-Romero, Francisco Javier Jiménez-Albericio, Isabel Marzo, Javier Naval, Alberto Anel","doi":"10.1080/2162402X.2025.2559782","DOIUrl":"10.1080/2162402X.2025.2559782","url":null,"abstract":"<p><p>Adoptive cell therapy and the use of monoclonal antibodies are two therapeutic modalities implemented in the treatment of multiple myeloma (MM). In this study, we combined the anti-CD38 therapeutic mAb daratumumab with different types of NK cells, leveraging the antibody-dependent cell-mediated cytotoxicity (ADCC) performed by these immune cells. Daratumumab was initially combined with activated and expanded NK cells (eNK), resulting in significant cytotoxic activity against human MM cell lines. As an alternative model to minimize the variability among donors of NK cells, the NK92 cell line was used, which showed greater cytotoxic activity than eNK cells against MM cell lines. However, since NK92 cells lacked CD16 receptor expression, they could not be used in combination with mAbs. To circumvent this, we performed a CD16 transfection on NK92 cells, generating the stable NK92-CD16 cell line. These cells were tested in combination with daratumumab against human MM cell lines with excellent results under various conditions, such as 2D and 3D cultures, even at very low effector-to-target ratios. NK92-CD16 cells were then tested in the presence of daratumumab against plasma cells from MM patients, with anti-myeloma activity even against cells from relapsed patients. <i>In vivo</i> experiments using MM xenografts or intravenous injection of MM cells in NGS mice, followed by treatment with NK92-CD16 cells in the presence or absence of daratumumab showed tumor regressions, especially in the second model, with nearly complete elimination of the MM cells when NK92-CD16 cells were combined with daratumumab.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2559782"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139069","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 the immune landscape in healthy mouse prostate and during prostate cancer progression.","authors":"Despoina Pervizou, Joanna De Chiara, Lionel Spinelli, Maïa Nestor-Martin, Lionel Chasson, Kateryna Len-Tayon, Darya Yanushko, Frédéric Fiore, Marc Bajénoff, Bernard Malissen, Daniel Metzger, Gilles Laverny, Sandrine Henri","doi":"10.1080/2162402X.2025.2562220","DOIUrl":"10.1080/2162402X.2025.2562220","url":null,"abstract":"<p><p>The immune landscape of healthy prostate and its alterations during prostate cancer (PCa) progression remain poorly characterized. Using scRNA-sequencing and multiparametric flow-cytometry analysis, we comprehensively characterized immune cells in wild-type and PTEN^(i)pe-/- mouse prostates, a model that closely recapitulates human PCa. PCa in PTEN^(i)pe-/- is marked by the recruitment of tumor-associated neutrophils (TANs), which represent the dominant immune cell population and resolved into eight distinct states, Trem2⁺ tumor-associated-macrophages (TAMs), and exhausted CD8⁺ T cells. Trem2⁺ TAMs differ from the three main resident macrophage populations in the healthy prostate, exhibiting a strong metabolic and immunosuppressive signature, likely driven by the MIF/HIF1A-signaling axis. This study provides the first detailed characterization of immune cells in the healthy mouse prostate and reveals changes in the immune landscape associated with prostate cancer progression.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2562220"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/2162402X.2024.2444174","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2444174","url":null,"abstract":"","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2444174"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899508","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":"Partial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112.","authors":"Ruth Soler-Agesta, Manuel Beltrán-Visiedo, Ai Sato, Takahiro Yamazaki, Emma Guilbaud, Christina Y Yim, Maria T Congenie, Tyler D Ames, Alberto Anel, Lorenzo Galluzzi","doi":"10.1080/2162402X.2025.2507245","DOIUrl":"10.1080/2162402X.2025.2507245","url":null,"abstract":"<p><p>PT-112 is a novel small molecule exhibiting promising clinical activity in patients with solid tumors. PT-112 kills malignant cells by inhibiting ribosome biogenesis while promoting the emission of immunostimulatory signals. Accordingly, PT-112 is an authentic immunogenic cell death (ICD) inducer and synergizes with immune checkpoint inhibitors in preclinical models of mammary and colorectal carcinoma. Moreover, PT-112 monotherapy has led to durable clinical responses, some of which persisting after treatment discontinuation. Mitochondrial outer membrane permeabilization (MOMP) regulates the cytotoxicity and immunogenicity of various anticancer agents. Here, we harnessed mouse mammary carcinoma TS/A cells to test whether genetic alterations affecting MOMP influence PT-112 activity. As previously demonstrated, PT-112 elicited robust antiproliferative and cytotoxic effects against TS/A cells, which were preceded by the ICD-associated exposure of calreticulin (CALR) on the cell surface, and accompanied by the release of HMGB1 in the culture supernatant. TS/A cells responding to PT-112 also exhibited eIF2α phosphorylation and cytosolic mtDNA accumulation, secreted type I IFN, and exposed MHC Class I molecules as well as the co-inhibitory ligand PD-L1 on their surface. Acute cytotoxicity and HMGB1 release caused by PT-112 in TS/A cells were influenced by MOMP competence. Conversely, PT-112 retained antiproliferative effects and its capacity to drive type I IFN secretion as well as CALR, MHC Class I and PD-L1 exposure on the cell surface irrespective of MOMP defects. These data indicate a partial involvement of MOMP in the mechanisms of action of PT-112, suggesting that PT-112 is active across various tumor types, including malignancies with MOMP defects.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2507245"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095303","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}