Oncoimmunology最新文献

{"title":"Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137.","authors":"Rui Sun, Kang Yi Lee, Yu Mei, Emily Nickles, Jia Le Lin, Runze Xia, Haiyan Liu, Herbert Schwarz","doi":"10.1080/2162402X.2024.2443265","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2443265","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers. Further, CD137 is expressed by malignant cells of certain cancers, making it a potential target for tumor immunotherapy. Here, we report the development of a fully human anti-human CD137 antibody of the IgG1 isotype, clone P1A1, that induces antibody-dependent cell-mediated cytotoxicity (ADCC) in CD137⁺ Tregs and cancer cells. P1A1 cross-reacts with murine CD137 which allowed testing murine chimeric P1A1 in syngeneic murine tumor models where P1A1 significantly reduced the number of CD137⁺ Tregs and inhibited tumor growth in a murine hepatocellular carcinoma (HCC) and a melanoma lung metastasis model. P1A1 can also be internalized thus enabling it as a carrier for drugs to target CD137⁺ Tregs and cancer cells. These anti-cancer properties suggest a translation of P1A1 to human immunotherapy.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2443265"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883138","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":"Circulating cytokine associations with clinical outcomes in melanoma patients treated with combination nivolumab plus ipilimumab.","authors":"Jiajia Chen, Giuseppe Tarantino, Mariano Severgnini, Joanna Baginska, Anita Giobbie-Hurder, Jason L Weirather, Michael Manos, Janice D Russell, Kathleen L Pfaff, Scott J Rodig, Amy Y Huang, Ryan Brennick, Matthew Nazzaro, Emma Hathaway, Marta Holovatska, Claire Manuszak, Srinika Ranasinghe, David Liu, F Stephen Hodi","doi":"10.1080/2162402X.2024.2432723","DOIUrl":"10.1080/2162402X.2024.2432723","url":null,"abstract":"<p><p>Nivolumab plus ipilimumab (aCTLA-4/aPD-1) combination therapy has significantly improved clinical outcomes in patients with metastatic melanoma, with 50%-60% of patients responding to treatment, but predictors of response are poorly characterized. We hypothesized that circulating cytokines and peripheral white blood cells may predict response to therapy and evaluated 15 cytokines and complete blood counts (CBC with differentials) from 89 patients with advanced melanoma treated with combination therapy from three points in time: pre-treatment, one month and approximately three months after starting therapy. Clinical endpoints evaluated included durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS). A parsimonious predictive model was developed to identify cytokines predictors of response to combination therapy. In this study, we found that pre-treatment, patients with DCB had higher IL-23, lower CXCL6, and lower IL-10 levels. Lower NLR one month after starting therapy predicted better PFS and OS, primarily driven by an increase in absolute lymphocytes. A multivariate model demonstrated that baseline CXCL6, IL-10, IL-23 were independent predictors of therapy response, and the combined model has reached an area under the curve (AUC) of 0.79 in prediction of response to combination therapy. Our study identified baseline CXCL6, IL-23, and IL-10 as predictors of response to aCTLA4/aPD1 combination therapy among patients with metastatic melanoma. This study also provides a framework for identifying patients who are likely to respond to combination ICB, as well as a subset of patients with high risk of developing resistance and are thus in need of alternative therapeutic options, such as clinical trials.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2432723"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immune checkpoint LAG-3 is expressed by melanoma cells and correlates with clinical progression of the melanoma.","authors":"Melanie Wiecken, Devayani Machiraju, Shounak Chakraborty, Eva-Maria Mayr, Bénédicte Lenoir, Rosa Eurich, Jasmin Richter, Nicole Pfarr, Niels Halama, Jessica C Hassel","doi":"10.1080/2162402X.2024.2430066","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2430066","url":null,"abstract":"<p><p>Immune checkpoint blockers have substantially improved prognosis of melanoma patients, nevertheless, resistance remains a significant problem. Here, intrinsic and extrinsic factors in the tumor microenvironment are discussed, including the expression of alternative immune checkpoints such as lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). While most studies focus on immune cell expression of these proteins, we investigated their melanoma cell intrinsic expression by immunohistochemistry in melanoma metastases of 60 patients treated with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy, and correlated it with the expression of potential ligands, RNA sequencing data and clinical outcome. LAG-3 and TIM-3 were commonly expressed in melanoma cells. In the stage IV cohort, expression of LAG-3 was associated with M1 stage (<i>p</i> < 0.001) and previous exposure to immune checkpoint inhibitors (<i>p</i> = 0.029). Moreover, in the anti-PD-1 monotherapy treatment group patients with high LAG-3 expression by tumor cells tended to have a shorter progression-free survival (<i>p</i> = 0.088), whereas high expression of TIM-3 was associated with a significantly longer overall survival (<i>p</i> = 0.007). In conclusion, we provide a systematic analysis of melanoma cell intrinsic LAG-3 and TIM-3 expression, highlighting potential implications of their expression on patient survival.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2430066"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883141","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":"Calpain 2 regulates IL-1α secretion and inhibits tumor development via modulating calpain 1 expression in the tumor microenvironment.","authors":"Zuhairah Binte Hanafi, Yu Mei, Huey Yee Teo, Ying Zhu, Chew Chin Yong Lionel, Jing Wen Chiu, Jinhua Lu, Haiyan Liu","doi":"10.1080/2162402X.2025.2451444","DOIUrl":"10.1080/2162402X.2025.2451444","url":null,"abstract":"<p><p>Tumor-promoting inflammation significantly impacts cancer progression, and targeting inflammatory cytokines has emerged as a promising therapeutic approach in clinical trials. Interleukin (IL)-1α, a member of the IL-1 cytokine family, plays a crucial role in both inflammation and carcinogenesis. How IL-1α is secreted in the tumor microenvironment has been poorly understood, and we previously showed that calpain 1 cleaves pro-IL-1α for mature IL-1α secretion, which exacerbates hepatocellular carcinoma by recruiting myeloid-derived suppressor cells. In this study, we report that calpain 2 also modulates IL-1α secretion. Notably, a deficiency in calpain 2 resulted in enhanced hepatocellular carcinoma development within an IL-1α-enriched tumor microenvironment. Further investigations revealed that calpain 2 deficiency increased calpain 1 expression, implying a compensatory mechanism between the two calpains. Mechanistically, calpain 2 deficiency led to increased expression of FoxO3, which is a forkhead transcription factor that promotes calpain 1 expression. Collectively, these results suggest that calpain 2 modulates calpain 1 expression, and therefore IL-1α secretion through the induction of FoxO3, offering novel potential therapeutic targets for cancer treatment.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2451444"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972859","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":"Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers.","authors":"Miriam Velasco-Sidro, Javier Arroyo-Ródenas, Laura Díez-Alonso, Ángel Ramírez-Fernández, Luis Álvarez-Vallina","doi":"10.1080/2162402X.2024.2444701","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2444701","url":null,"abstract":"<p><p>Despite recent advances in immunotherapy against B cell malignancies such as BCMA (B cell maturation antigen) and CD19-targeted treatments using soluble T cell-engaging (TCE) antibodies or chimeric antigen receptor T cells (CAR-T), there is still an important number of patients experiencing refractory/relapsed (R/R) disease. Approaches to avoid tumor-intrinsic mechanisms of resistance such as immune pressure-mediated antigen downmodulation, are being broadly investigated. These strategies include BCMA/CD19 dual-targeting therapies, which may be of particular interest to patients with B cell lymphoma and multiple myeloma, where a specific double-positive immature subpopulation is commonly associated with poor prognosis and poor response to current treatments. In fact, several clinical trials targeting both antigens through different strategies are currently underway. Here, based on the previously validated STAb (in situ secretion of T cell-redirecting bispecific antibodies) concept, we used two different engineering strategies (pool and co-transduction) to generate dual-targeted STAb-T cells simultaneously secreting BCMA TCE and CD19 TCE that outperformed single-targeted STAb-T cells in different <i>in vitro</i> models. These promising results encourage further preclinical clinical testing of dual STAb-T cells in R/R B-cell malignancies.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2444701"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899531","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":"Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7^th immunorad conference.","authors":"Pierre-Antoine Laurent, Fabrice André, Alexandre Bobard, Desiree Deandreis, Sandra Demaria, Stephane Depil, Stefan B Eichmüller, Cristian Fernandez-Palomo, Floris Foijer, Lorenzo Galluzzi, Jérôme Galon, Matthias Guckenberger, Kevin J Harrington, Fernanda G Herrera, Peter E Huber, Antoine Italiano, Sana D Karam, Guido Kroemer, Philippe Lambin, Carola Leuschner, Alberto Mantovani, Etienne Meylan, Michele Mondini, Mikael J Pittet, Jean-Pierre Pouget, Jordi Remon, Claus S Sørensen, Christos Sotiriou, Claire Vanpouille-Box, Ralph R Weichselbaum, James W Welsh, Laurence Zitvogel, Silvia C Formenti, Eric Deutsch","doi":"10.1080/2162402X.2024.2432726","DOIUrl":"10.1080/2162402X.2024.2432726","url":null,"abstract":"<p><p>Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer. Herein, we report on the topics developed by key-opinion leaders during the 7^th Immunorad Conference held in Paris-Les Cordeliers (France) from September 27th to 29th 2023, and set the stage for the 8^th edition of Immunorad which will be held at Weill Cornell Medical College (New-York, USA) in October 2024.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2432726"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856327","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":"Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors.","authors":"Chang Sook Hong, Elizabeth V Menchikova, Yana Najjar, Theresa L Whiteside, Edwin K Jackson","doi":"10.1080/2162402X.2024.2444704","DOIUrl":"https://doi.org/10.1080/2162402X.2024.2444704","url":null,"abstract":"<p><p>The adenosinergic pathway converting endogenous ATP to adenosine (ADO) is a major immunosuppressive pathway in cancer. Emerging data indicate that plasma small extracellular vesicles (sEV) express CD39 and CD73 and produce ADO. Using a noninvasive, highly sensitive newly developed assay, metabolism of N⁶-etheno-labeled eATP, eADP or eAMP by ecto-nucleotidases on the external surface of sEV was measured using high pressure liquid chromatography with fluorescence detection. Ecto-nucleotidase activity in sEV isolated from plasma of randomly selected cancer patients and healthy donors (HDs) was compared. Relative to sEV of HDs, sEV from the plasma of melanoma patients metabolized eATP to eADP and eAMP to eADO with significantly greater efficiency. Activities of both CD39 and CD73 were elevated, as determined by the use of pharmacologic inhibitors selective for these enzymes. In contrast, metabolic activity of CD39 and CD73 on sEV isolated from plasma of patients with head and neck cancer was comparable to that of HDs, suggesting that the activity of ecto-nucleotidases on sEV may differ depending on the cancer type or cancer stage. The N⁶-etheno-purine assay measuring contributions of ecto-nucleotidases residing on the surface of sEV to the extracellular ATP to ADO pathway can discriminate cancer patients from HDs, differentiate among different cancer types, and potentially identify patients most likely to benefit from anti-adenosinergic therapy designed to inhibit the adenosine-mediated immune suppression.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2444704"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865895","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":"Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system.","authors":"Yukie Ando, Yutaka Horiuchi, Sara Hatazawa, Momo Mataki, Akihiro Nakamura, Takashi Murakami","doi":"10.1080/2162402X.2024.2437211","DOIUrl":"10.1080/2162402X.2024.2437211","url":null,"abstract":"<p><p>Accumulating evidence suggests that phenotype switching of cancer cells is essential for therapeutic resistance. However, the immunological characteristics of drug-induced phenotype-switching melanoma cells (PSMCs) are unknown. We investigated PSMC elimination by host immunity using hyperdifferentiated melanoma model cells derived from murine B16F10 melanoma cells. Exposure of B16F10 cells to staurosporine induced a hyperdifferentiated phenotype associated with transient drug tolerance. Staurosporine-induced hyperdifferentiated B16F10 (sB16F10) cells expressed calreticulin on their surface and were phagocytosed efficiently. Furthermore, the inoculation of mice with sB16F10 cells induced immune responses against tumor-derived antigens. Despite the immunogenicity of sB16F10 cells, they activated the PD-1/PD-L1 immune checkpoint system and strongly resisted T cell-mediated tumor destruction. However, <i>in vivo</i> treatment with immune checkpoint inhibitors successfully eliminated the tumor. Thus, hyperdifferentiated melanoma cells have conflicting immunological properties - enhanced immunogenicity and immune evasion. Inhibiting the ability of PSMCs to evade T cell-mediated elimination might lead to complete melanoma eradication.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2437211"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796568","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":"Paradoxical control of multifocal mammary oncogenesis by radiation therapy.","authors":"Lorenzo Galluzzi, Aitziber Buqué","doi":"10.1080/2162402X.2025.2458886","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2458886","url":null,"abstract":"<p><p>In an immunocompetent mouse model of multifocal, metachronous HR⁺ mammary carcinogenesis, we have recently demonstrated that a superior control of primary neoplastic lesions by focal radiotherapy does not necessarily translate into improved oncosuppression at non-irradiated (pre)malignant tissues. These data point to a link between local tumor control by radiotherapy and systemic oncogenesis that remains to be fully understood.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2458886"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053977","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}