Oncoimmunology最新文献_第2页

Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-02-18 DOI: 10.1080/2162402X.2025.2466308

Daniel A Ruiz-Torres, Michael E Bryan, Shun Hirayama, Ross D Merkin, Evelyn Luciani, Thomas J Roberts, Manisha Patel, Jong C Park, Lori J Wirth, Peter M Sadow, Moshe Sade-Feldman, Shannon L Stott, Daniel L Faden

{"title":"Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma.","authors":"Daniel A Ruiz-Torres, Michael E Bryan, Shun Hirayama, Ross D Merkin, Evelyn Luciani, Thomas J Roberts, Manisha Patel, Jong C Park, Lori J Wirth, Peter M Sadow, Moshe Sade-Feldman, Shannon L Stott, Daniel L Faden","doi":"10.1080/2162402X.2025.2466308","DOIUrl":"10.1080/2162402X.2025.2466308","url":null,"abstract":"Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The combined positive score (CPS) for PD-L1 is the only biomarker approved to predict response to ICB and has limited performance. Tertiary Lymphoid Structures (TLS) have shown promising potential for predicting response to ICB. However, their exact composition, size, and spatial biology in HNSCC remain understudied. To elucidate the impact of TLS spatial biology in response to ICB, we utilized pre-ICB tumor tissue sections from 9 responders (complete response, partial response, or stable disease) and 11 non-responders (progressive disease) classified via RECISTv1.1. A custom multi-immunofluorescence (mIF) staining assay was applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblasts (α Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). A machine learning model was employed to measure the effect of spatial metrics on achieving a response to ICB. A higher density of B cells (CD20+) was found in responders compared to non-responders to ICB (p = 0.022). The presence of TLS within 100 µm of the tumor was associated with improved overall (p = 0.04) and progression-free survival (p = 0.03). A multivariate machine learning model identified TLS density as a leading predictor of response to ICB with 80% accuracy. Immune cell densities and TLS spatial location play a critical role in the response to ICB in HNSCC and may potentially outperform CPS as a predictor of response.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2466308"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442459","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}

引用次数: 0

A targeted MAVS fusion protein for controlled innate immune activation and antitumor therapy.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-03-14 DOI: 10.1080/2162402X.2025.2478850

Muhan Wang, Zhijie Zhang, YouYou Yang, Xiaoyi Peng, Hongping Yin

{"title":"A targeted MAVS fusion protein for controlled innate immune activation and antitumor therapy.","authors":"Muhan Wang, Zhijie Zhang, YouYou Yang, Xiaoyi Peng, Hongping Yin","doi":"10.1080/2162402X.2025.2478850","DOIUrl":"10.1080/2162402X.2025.2478850","url":null,"abstract":"Targeted therapies leveraging the innate immune system are emerging as promising cancer treatments. The mitochondrial antiviral signaling protein (MAVS) plays a crucial role in initiating innate immune responses, but its clinical use is limited by the risk of uncontrolled activation and systemic toxicity. To address this, we developed a novel therapeutic agent, the truncated interferon activation switch (TRIAS), combining MAVS truncates with a tumor antigen-targeting single-chain variable fragment (scFv). This design ensures antigen-dependent, controlled activation. Lentiviral delivery of TRIAS induced significant antitumor responses, including complete tumor regression in some cases. Flow cytometry (FCM) analysis further confirmed that tumor cells were the predominant population expressing the transgene. TRIAS-expressing tumor cells exhibited enhanced antitumor activity, likely due to increased cytokine release and upregulated major histocompatibility complex (MHC) expression, enabling tumor cells to function as antigen-presenting cells. This activated other immune cells, driving adaptive immune responses. Additionally, TRIAS promoted a proinflammatory shift in the tumor microenvironment (TME). In conclusion, TRIAS was validated as an innovative immunotherapeutic agent with MAVS-like immune-activating properties and tightly controlled mechanisms, offering a safer and more effective approach for clinical cancer immunotherapy.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2478850"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630951","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}

引用次数: 0

Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-03-17 DOI: 10.1080/2162402X.2025.2477872

Felipe F Lamenza, Peyton Roth, Puja Upadhaya, Suvekshya Shrestha, Sushmitha Jagadeesha, Natalie Kazmierowicz, Natalie Horn, Hasan Pracha, Sonali Dasari, Steve Oghumu

{"title":"Efficacy of anti-LAG3 and anti-PD-1 combination checkpoint inhibitor therapy against head and neck squamous cell carcinoma in a genetically engineered mouse model.","authors":"Felipe F Lamenza, Peyton Roth, Puja Upadhaya, Suvekshya Shrestha, Sushmitha Jagadeesha, Natalie Kazmierowicz, Natalie Horn, Hasan Pracha, Sonali Dasari, Steve Oghumu","doi":"10.1080/2162402X.2025.2477872","DOIUrl":"10.1080/2162402X.2025.2477872","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) continues to be among the most common malignancies worldwide with limited treatment options for patients. Targeting the PD-1/PDL-1 axis is currently the only FDA approved immune checkpoint inhibitor treatment for HNSCC. Novel therapies targeting other pathways are needed along with testing a combinational approach to find new and more efficient ways to treat this disease. We utilized a tamoxifen inducible TgfβR1/Pten deletion mouse model to explore the efficacy of combined anti-LAG-3 and anti-PD-1 therapy against tongue HNSCC and determine underlying immunological mechanisms. Combined anti-LAG-3/anti-PD-1 therapy was effective at decreasing the tumor burden and lymphatic metastasis compared to anti-LAG-3 treatment but not when compared to the anti-PD-1 treatment alone. Anti-tumoral effects of anti-PD1 and anti-LAG-3/anti-PD-1 combined therapy were associated with increased CD4+ and CD8+ T-cell proliferative responses in secondary lymphoid organs along with increased CD8+ T-cell tumor infiltration. Anti-LAG-3 treatment potentiated the anti-tumoral properties of CD4+ T-cells treated with anti-PD-1, including enhanced systemic IFN-γ production and TNF-α production in the tumor microenvironment. Further, anti-tumoral cytotoxic CD8+ T-cell effector function and granzyme B production were enhanced by anti-PD-1 and combinatorial anti-LAG-3/anti-PD-1 immunotherapy, resulting in greater tumor cell death. Our results demonstrate that anti-LAG-3 has the potential to enhance the efficacy of anti-PD-1 therapy; however, humanized mouse models that better recapitulate the human disease with FDA approved antibodies are needed to further characterize the efficacy of this treatment as a viable treatment option for HNSCC patients.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2477872"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651566","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}

引用次数: 0

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7^th immunorad conference. 推动放射治疗-免疫治疗联合的界限：第七届免疫大会的亮点。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2024-12-18 DOI: 10.1080/2162402X.2024.2432726

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

{"title":"Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7th 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":"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 7th Immunorad Conference held in Paris-Les Cordeliers (France) from September 27th to 29th 2023, and set the stage for the 8th edition of Immunorad which will be held at Weill Cornell Medical College (New-York, USA) in October 2024.","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}

引用次数: 0

Dual nanobody-redirected and Bi-specific CD13/TIM3 CAR T cells eliminate AML xenografts without toxicity to human HSCs.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/2162402X.2025.2458843

Xuyao Zhang, Zijie Feng, Annapurna Pranatharthi Haran, Xianxin Hua

{"title":"Dual nanobody-redirected and Bi-specific CD13/TIM3 CAR T cells eliminate AML xenografts without toxicity to human HSCs.","authors":"Xuyao Zhang, Zijie Feng, Annapurna Pranatharthi Haran, Xianxin Hua","doi":"10.1080/2162402X.2025.2458843","DOIUrl":"10.1080/2162402X.2025.2458843","url":null,"abstract":"Adoptive cell therapy including chimeric antigen receptor (CAR) T cells targeting CD19 has been approved by FDA to treat B cell-derived malignancies with remarkable success. The success has not yet been expanded to treating Acute Myeloid Leukemia (AML). We previously showed that a nanobody and single-chain fragment variable (scFv) CD13 (Nanobody)/TIM-3 (scFv) directed bispecific split CAR (bissCAR) T cells, while effective in eliminating AML in preclinical models, also caused substantial toxicity to human hematopoietic stem cells (HSCs) and other lineages. To maintain the bissCART specificity and efficacy, yet reduce toxicity to normal cells including HSCs, we generated new anti-TIM-3 nanobodies and constructed new cognate nanobodies-directed CD13/41BB and TIM3/CD3zeta nbiCARTs. The resultant nbiCARTs showed strong antitumor activity to CD13/TIM3 positive leukemic cells in vitro and in preclinical models. Importantly, the 3rd generation of nbiCARTs had little toxicity to human bone marrow-derived colony forming progenitors ex vivo and the human HSCs in mice with a humanized immune system. Together, the current studies generated novel and 3rd G CD13/TIM-3 nbiCARTs that displayed stronger antitumor activity yet minimal toxicity to normal tissues like HSCs that express a moderate level of CD13, paving the way to further evaluate the novel CD13/TIM-3CARTs in treating aggressive and refractory AML in clinical studies.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2458843"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460342","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}

引用次数: 0

Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-02-04 DOI: 10.1080/2162402X.2025.2457793

Maria Paula Roberti, Pornpimol Charoentong, Yanhong Lyu, Marten Meyer, Stefan B Eichmüller, Patrick Schmidt, Frank Momburg, Miray Cetin, Felix Hartmann, Nektarios A Valous, Albrecht Stenzinger, Laura Michel, Peter Lichter, Andreas Schneeweiss, Verena Thewes, Carlo Fremd, Inka Zörnig, Dirk Jäger

{"title":"Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site.","authors":"Maria Paula Roberti, Pornpimol Charoentong, Yanhong Lyu, Marten Meyer, Stefan B Eichmüller, Patrick Schmidt, Frank Momburg, Miray Cetin, Felix Hartmann, Nektarios A Valous, Albrecht Stenzinger, Laura Michel, Peter Lichter, Andreas Schneeweiss, Verena Thewes, Carlo Fremd, Inka Zörnig, Dirk Jäger","doi":"10.1080/2162402X.2025.2457793","DOIUrl":"10.1080/2162402X.2025.2457793","url":null,"abstract":"T cells that recognize tumor-specific mutations are crucial for cancer immunosurveillance and in adoptive transfer of TILs or transgenic-TCR T cell products. However, their challenging identification and isolation limits their use in clinical practice. Therefore, novel approaches to isolate tumor-specific T cells are needed. Here, we report the isolation of neoantigen-specific CD8+ T cells from a vaccination site of a metastatic breast cancer patient who received a personalized vaccine. Based on the somatic mutations, potential MHC binding epitopes were predicted, of which 17 were selected to generate a peptide vaccine. Cutaneous biopsies were processed after the fifth vaccination cycle to obtain infiltrating lymphocytes from the vaccination site (VILs). IFNγ ELISpot revealed reactivity to four peptides used in the vaccine. Reactive T cells from VILs were non-overlapping with those detected in the blood and the tumor-microenvironment. ScTCR Seq analysis revealed the presence of a clonotype in VILs that further expanded after a round of in vitro stimulation and validated to be specific against a private mutation, namely NCOR1L1475R, presented in the context of HLA-B * 07:02, with no reactivity to the wild-type peptide. Our study shows, for the first time, that tumor mutation - specific T cells are generated at high frequencies in the vaccination site and can be isolated with standard methods for TCR screening. The easy and safe accessibility of skin biopsies overcomes the major hurdles of current TCR screening approaches and present exciting opportunities for the development of innovative immunotherapeutic strategies.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2457793"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190454","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}

引用次数: 0

Metabolic heterogeneity in tumor cells impacts immunology in lung squamous cell carcinoma.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-02-09 DOI: 10.1080/2162402X.2025.2457797

Qian Wang, Na Sun, Chaoyang Zhang, Thomas Kunzke, Philipp Zens, Annette Feuchtinger, Sabina Berezowska, Axel Walch

{"title":"Metabolic heterogeneity in tumor cells impacts immunology in lung squamous cell carcinoma.","authors":"Qian Wang, Na Sun, Chaoyang Zhang, Thomas Kunzke, Philipp Zens, Annette Feuchtinger, Sabina Berezowska, Axel Walch","doi":"10.1080/2162402X.2025.2457797","DOIUrl":"10.1080/2162402X.2025.2457797","url":null,"abstract":"Metabolic processes are crucial in immune regulation, yet the impact of metabolic heterogeneity on immunological functions remains unclear. Integrating metabolomics into immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. To elucidate such insight in lung squamous cell carcinoma (LUSC), we analyzed 106 LUSC tumor tissues. We performed high-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to obtain spatial metabolic profiles, and immunohistochemistry to detect tumor-infiltrating T lymphocytes (TILs). Unsupervised k-means clustering and Simpson's diversity index were employed to assess metabolic heterogeneity, identifying five distinct metabolic tumor subpopulations. Our findings revealed that TILs are specifically associated with metabolite distributions, not randomly distributed. Integrating a validation cohort, we found that heterogeneity-correlated metabolites interact with CD8+ TIL-associated genes, affecting survival. High metabolic heterogeneity was linked to worse survival and lower TIL levels. Pathway enrichment analyses highlighted distinct metabolic pathways in each subpopulation and their potential responses to chemotherapy. This study uncovers the significant impact of metabolic heterogeneity on immune functions in LUSC, providing a foundation for tailoring therapeutic strategies.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2457797"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383739","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}

引用次数: 0

Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-02-17 DOI: 10.1080/2162402X.2025.2466305

Rita Turpin, Karita Peltonen, Jenna H Rannikko, Ruixian Liu, Anita N Kumari, Daniel Nicorici, Moon Hee Lee, Minna Mutka, Panu E Kovanen, Laura Niinikoski, Tuomo Meretoja, Johanna Mattson, Petrus Järvinen, Kanerva Lahdensuo, Riikka Järvinen, Sara Tornberg, Tuomas Mirtti, Pia Boström, Ilkka Koskivuo, Anil Thotakura, Jeroen Pouwels, Maija Hollmén, Satu Mustjoki, Juha Klefström

{"title":"Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses.","authors":"Rita Turpin, Karita Peltonen, Jenna H Rannikko, Ruixian Liu, Anita N Kumari, Daniel Nicorici, Moon Hee Lee, Minna Mutka, Panu E Kovanen, Laura Niinikoski, Tuomo Meretoja, Johanna Mattson, Petrus Järvinen, Kanerva Lahdensuo, Riikka Järvinen, Sara Tornberg, Tuomas Mirtti, Pia Boström, Ilkka Koskivuo, Anil Thotakura, Jeroen Pouwels, Maija Hollmén, Satu Mustjoki, Juha Klefström","doi":"10.1080/2162402X.2025.2466305","DOIUrl":"10.1080/2162402X.2025.2466305","url":null,"abstract":"Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of the tumor immune microenvironment (TIME). Patient-derived ex vivo models contain authentic resident immune cells and therefore, could provide new mechanistic insights into how the TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two different ex vivo models of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism, while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as benchmarks for drug-induced immune activation in ex vivo models of the TIME. The robust reproducibility of immunomodulatory drug responses observed across diverse ex vivo models of the TIME underscores the significance of human patient-derived models in elucidating the complexities of anti-tumor immunity and therapeutic interventions.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2466305"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442456","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}

引用次数: 0

Cellular and secretome profiling uncover immunological biomarkers in the prognosis of renal cell carcinoma patients.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-03-24 DOI: 10.1080/2162402X.2025.2481109

Le Tong, Veronika Kremer, Shi Yong Neo, Christina Seitz, Nicholas P Tobin, Barbara Seliger, Ulrika Harmenberg, Eugenia Colón, Ann-Helén Scherman Plogell, Lisa L Liu, Andreas Lundqvist

{"title":"Cellular and secretome profiling uncover immunological biomarkers in the prognosis of renal cell carcinoma patients.","authors":"Le Tong, Veronika Kremer, Shi Yong Neo, Christina Seitz, Nicholas P Tobin, Barbara Seliger, Ulrika Harmenberg, Eugenia Colón, Ann-Helén Scherman Plogell, Lisa L Liu, Andreas Lundqvist","doi":"10.1080/2162402X.2025.2481109","DOIUrl":"10.1080/2162402X.2025.2481109","url":null,"abstract":"Renal cell carcinoma (RCC) is recognized as an immunogenic tumor, yet tumor-infiltrating lymphocytes often exhibit diminished effector function. However, the mechanisms underlying reduced T and NK cell activity in RCC remain unclear. Here, we examined the immune contexture in RCC patients undergoing nephrectomy to identify immune-related biomarkers associated with disease progression. Immune cell phenotypes and secretion profiles were assessed using flow cytometry and Luminex multiplex analysis. Supervised multivariate analysis revealed several changes of which frequencies of T and NK cells expressing CCR5, CXCR3, and PD-1 were elevated within tumors compared with peripheral blood. In addition, higher levels of regulatory T cells, PD-1+, and CXCR3+ T and NK cells were observed in patients with relapse following nephrectomy. With regards to soluble factors, tumor-derived CXCL8 was associated with higher Fuhrman grade and increased frequency of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). These biomarkers demonstrate potential relevance in the progression of RCC and merit further investigation in prospective studies.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2481109"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694133","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}

引用次数: 0

EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity.

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-04-07 DOI: 10.1080/2162402X.2025.2485535

Lola Boutin, Mingzhi Liu, Julie Déchanet Merville, Oscar Bedoya-Reina, Margareta T Wilhelm

{"title":"EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity.","authors":"Lola Boutin, Mingzhi Liu, Julie Déchanet Merville, Oscar Bedoya-Reina, Margareta T Wilhelm","doi":"10.1080/2162402X.2025.2485535","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2485535","url":null,"abstract":"Medulloblastoma (MB) is a pediatric brain tumor that develops in the cerebellum, representing one of the most common malignant brain cancers in children. Standard treatments include surgery, chemotherapy, and radiation, but despite a 5-y survival rate of approximately 70%, these therapies often lead to significant neurological damage in the developing brain. This underscores the urgent need for less toxic, more effective therapeutic alternatives. Recent advancements in cancer immunotherapy, including immune checkpoint inhibitors and CAR-T cell therapy, have revolutionized cancer treatment. One promising avenue is the use of Gamma Delta (γδ)T cells, a unique T cell population with potential advantages, such as non-alloreactivity, potent tumor cell lysis, and broad antigen recognition. However, their capacity to recognize and target MB cells remains underexplored. To investigate the therapeutic potential of γδT cells against MB, we analyzed the proportion and status of MB-infiltrated γδT cells within patient datasets. We next investigated the expression of γδT cell ligands on MB cells and identified the EphA2 receptor and the phosphoantigen/Butyrophilin complex as key ligands, activating Vγ9 Vδ1 and Vγ9 Vδ2 T cells, respectively, leading to significant MB cell lysis in both monolayer and spheroid models. Importantly, preliminary safety data showed that γδT cells did not target differentiated neurons or neuroepithelial stem cells derived from induced pluripotent stem cells, underscoring the selectivity and safety of this approach. In conclusion, γδT cells trigger an efficient and specific killing of MB and would offer a promising novel therapeutic strategy.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2485535"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796884","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}

引用次数: 0