Oncoimmunology最新文献_第3页

Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses. 肿瘤免疫微环境的患者源性肿瘤外植体模型显示出不同的、可重复的免疫治疗反应。

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

Isolation of a tumor neoantigen specific CD8+ TCR from a skin biopsy of a vaccination site. 从接种部位皮肤活检中分离肿瘤新抗原特异性CD8+ TCR。

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

Dual nanobody-redirected and Bi-specific CD13/TIM3 CAR T cells eliminate AML xenografts without toxicity to human HSCs. 双纳米体重定向和双特异性CD13/TIM3 CAR - T细胞消除AML异种移植物，对人造血干细胞无毒。

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

Novel immunodominant neoepitope in a KPC mouse model of pancreatic cancer allowing identification of tumor-specific T cells. 胰腺癌KPC小鼠模型中新的免疫显性新表位允许识别肿瘤特异性T细胞。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-04-08 DOI: 10.1080/2162402X.2025.2489815

Maria Antsiferova, Marco Berrera, Anne-Claire Zagdoun, Maha Raauf, Thuy Trinh Nguyen, Claudio Murgia, Birte Appelt, Christine Trumpfheller, Stephan Gasser, Sylvain Pilet, Valeria Nicolini, Ines Grazina de Matos

{"title":"Novel immunodominant neoepitope in a KPC mouse model of pancreatic cancer allowing identification of tumor-specific T cells.","authors":"Maria Antsiferova, Marco Berrera, Anne-Claire Zagdoun, Maha Raauf, Thuy Trinh Nguyen, Claudio Murgia, Birte Appelt, Christine Trumpfheller, Stephan Gasser, Sylvain Pilet, Valeria Nicolini, Ines Grazina de Matos","doi":"10.1080/2162402X.2025.2489815","DOIUrl":"10.1080/2162402X.2025.2489815","url":null,"abstract":"The 4662 KPC model is one of the most widely used mouse models of pancreatic cancer. It represents an excluded immune phenotype and closely recapitulates the pathophysiology of pancreatic cancer in humans. We set out to identify the endogenous neoepitopes present in 4662 cells. By combining whole-exome and RNA-sequencing and a bioinformatic neoantigen prediction pipeline, we have identified 15 potential candidate neoantigen epitopes. Ten more highly expressed were selected for validation in an in vivo vaccination study with 4662-tumor bearing mice. The Mrps35-derived neoantigen was found to be immunogenic as we have identified endogenous T-cells responding to this neoepitope, and the response was significantly increased upon vaccination with a synthetic peptide and upon PD1-IL2v therapy. Dextramers based on this peptide were validated and can be used to monitor endogenous tumor-specific CD8+ T-cells in response to immunotherapy. This will support the development of novel therapies for this highly unmet medical need indication.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2489815"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812686","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. 肿瘤细胞代谢异质性影响肺鳞状细胞癌的免疫学。

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

Smad7 is a negative regulator of immunogenic cell death in colorectal cancer. Smad7是结直肠癌中免疫原性细胞死亡的负调节因子。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-04-11 DOI: 10.1080/2162402X.2025.2490346

Claudia Maresca, Eleonora Franzè, Federica Laudisi, Marco Colella, Andrea Iannucci, Rachele Frascatani, Ivan Monteleone, Carmine Stolfi, Giovanni Monteleone

{"title":"Smad7 is a negative regulator of immunogenic cell death in colorectal cancer.","authors":"Claudia Maresca, Eleonora Franzè, Federica Laudisi, Marco Colella, Andrea Iannucci, Rachele Frascatani, Ivan Monteleone, Carmine Stolfi, Giovanni Monteleone","doi":"10.1080/2162402X.2025.2490346","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2490346","url":null,"abstract":"Induction of endoplasmic reticulum (ER) stress is followed by exposure of calreticulin (CRT) on the cancer cell plasma membrane and elicits an anticancer immune response, referred to as immunogenic cell death (ICD). Smad7 is highly expressed by colorectal cancer (CRC) cells, and its knockdown with a specific antisense oligonucleotide (AS) induces ER stress. We hypothesized that, by preventing ER stress, high Smad7 in CRC cells can contribute to limiting ICD. This study aimed to investigate whether targeted inhibition of Smad7 in CRC cells promotes an anti-cancer immune response. Downregulation of Smad7 in the human HCT116 and DLD1 cells and murine CT26 cells promoted calreticulin translocation to the plasma membrane and this phenomenon was prevented by Tauro-urso-deoxycholic acid, an inhibitor of ER stress. Smad7-deficient cells secreted high levels of ATP and HMGB1, thereby promoting the activation of co-cultured dendritic cells. Mice engrafted with Smad7-deficient CT26 cells developed fewer and smaller tumors than wild-type CT26 cell-engrafted mice and exhibited a marked tumor infiltration with CD8+ cells and to a lesser extent CD4+ cells. Depletion of CD8+ T cells abrogated the inhibitory effect of Smad7 knockdown on the tumor volume. Finally, we showed that, in a vaccination model, implanted Smad7-deficient CT26 cells protected mice from the development of tumors induced by wild-type CT26 cells. These data show that Smad7 deficiency triggers ICD in CRC cells, thus reducing tumor development and growth, and suggest that Smad7 inhibitors could be developed as novel ICD inducers, providing a new concept for antitumor immunotherapy.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2490346"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047781","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

EphA2 and phosphoantigen-mediated selective killing of medulloblastoma by γδT cells preserves neuronal and stem cell integrity. EphA2和磷抗原介导的γδT细胞选择性杀伤成神经管细胞瘤可保留神经元和干细胞的完整性。

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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980450/pdf/","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":"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. 细胞和分泌组分析揭示了肾细胞癌患者预后中的免疫生物标志物。

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

Updates on radiotherapy-immunotherapy combinations: Proceedings of 8th Annual ImmunoRad Conference. 放射治疗-免疫治疗联合疗法的最新进展：第八届年度免疫大会论文集。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-05-22 DOI: 10.1080/2162402X.2025.2507856

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

{"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":"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.","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}

引用次数: 0

Patritumab deruxtecan induces immunogenic cell death. Patritumab deruxtecan诱导免疫原性细胞死亡。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-06-03 DOI: 10.1080/2162402X.2025.2514050

Sabrina Forveille, Liwei Zhao, Allan Sauvat, Giulia Cerrato, Marion Leduc, Flora Doffe, Yuhong Pan, Peng Liu, Guido Kroemer, Oliver Kepp

{"title":"Patritumab deruxtecan induces immunogenic cell death.","authors":"Sabrina Forveille, Liwei Zhao, Allan Sauvat, Giulia Cerrato, Marion Leduc, Flora Doffe, Yuhong Pan, Peng Liu, Guido Kroemer, Oliver Kepp","doi":"10.1080/2162402X.2025.2514050","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2514050","url":null,"abstract":"Antibody-drug conjugates (ADCs) enable targeted delivery of cytotoxic payload to cancer cells. Here, we characterized the mode of action of the ADC patritumab deruxtecan, which is a monoclonal antibody specific for Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3, best known as HER3) coupled to the topoisomerase-I inhibitor DXd. Patritumab deruxtecan decreased viability and induced the relocation of calreticulin fused to green fluorescent protein (CALR-GFP) to the periphery of human osteosarcoma U2OS cells engineered to express HER3 but not in their parental counterparts only expressing the CALR-GFP biosensor. Patritumab deruxtecan as well as its payload DXd induced various traits of immunogenic cell death (ICD) including antibody detectable calreticulin membrane exposure, exodus of high mobility group protein B1 (HMGB1), as well as the release of ATP into cell culture supernatants. Moreover, DXd causes rapid inhibition of DNA-to-RNA transcription, which is a key predictor for ICD. Mouse cancer cells treated with DXd were able to vaccinate syngeneic immunocompetent mice against tumor challenge. Tumor-free mice developed immune memory that led to the rejection of syngeneic tumors after rechallenge. In conclusion, patritumab deruxtecan is equipped with a cytotoxic payload that induces hallmarks of ICD in vitro and elicits antitumor immunity in vivo.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2514050"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209977","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}

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