Oncoimmunology最新文献_第4页

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}

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

Combining local cytokine delivery and systemic immunization with recombinant artLCMV boosts antitumor efficacy in several preclinical tumor models. 重组artLCMV结合局部细胞因子传递和全身免疫，在几种临床前肿瘤模型中增强了抗肿瘤效果。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-06-10 DOI: 10.1080/2162402X.2025.2514040

Kimberly Pojar, Diana Reckendorfer, Judith Strauss, Sarah Szaffich, Sarah Ahmadi-Erber, Timo Schippers, Pedro Berraondo, Klaus K Orlinger, Josipa Raguz, Henning Lauterbach

{"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":"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.","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}

引用次数: 0

Correction. 修正。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2024-12-27 DOI: 10.1080/2162402X.2024.2444174

引用次数: 0

Partial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112. 部分线粒体参与PT-112的抗增殖和免疫刺激作用。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-05-19 DOI: 10.1080/2162402X.2025.2507245

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

{"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":"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.","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}

引用次数: 0

Potent immune-dependent anticancer effects of the non-cardiotoxic anthracycline aclarubicin. 无心脏毒性的蒽环类克拉霉素的免疫依赖性强效抗癌作用。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-06-04 DOI: 10.1080/2162402X.2025.2515176

Giulia Cerrato, Allan Sauvat, Mahmoud Abdellatif, Guido Kroemer

{"title":"Potent immune-dependent anticancer effects of the non-cardiotoxic anthracycline aclarubicin.","authors":"Giulia Cerrato, Allan Sauvat, Mahmoud Abdellatif, Guido Kroemer","doi":"10.1080/2162402X.2025.2515176","DOIUrl":"10.1080/2162402X.2025.2515176","url":null,"abstract":"Aclarubicin (also called aclacinomycin A) is an antineoplastic from the anthracycline class that is used in China and Japan but not in Europe nor in the USA. Aclarubicin induces much less DNA damage than the classical anthracyclines doxorubicin, daunorubicin, epirubicin, idarubicin, and the anthracene mitoxantrone, but is equally effective in inhibiting DNA-to-RNA transcription and in eliciting immunogenic stress in malignant cells. Accordingly, aclarubicin lacks the DNA damage-associated cardiotoxicity that is dose-limiting for classical anthracyclines. Conversely, aclarubicin is at least as potent as other anthracyclines in inducing immunogenic cell death (ICD), which is key for the mode of action of efficient chemotherapeutics. This combination of reduced toxicity and equivalent ICD-stimulatory activity may explain why, as compared to other anthracyclines, aclarubicin is particularly efficient against acute myeloid leukemia. As a result, we advocate for clinical studies seeking to replace the anthracyclines used in Western medicine by aclarubicin-like compounds. Such clinical studies should not only embrace hematological malignancies but should also concern solid cancers, including those in which ICD-inducing chemotherapies are followed by immunotherapies targeting the PD-1/PD-L1 interaction.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2515176"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217346","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

Uncovering common transcriptional features shared by mature peripheral blood PMN-MDSCs and tumor-infiltrating neutrophils in humans. 揭示人类成熟外周血PMN-MDSCs和肿瘤浸润中性粒细胞共有的转录特征。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-07-01 DOI: 10.1080/2162402X.2025.2521396

Chiara Lattanzi, Francisco Bianchetto-Aguilera, Marta Donini, Francesca Pettinella, Elena Caveggion, Monica Castellucci, Sara Gasperini, Barbara Mariotti, Ilaria Signoretto, Maurizio Cantini, Sara Pilotto, Lorenzo Belluomini, Cristina Tecchio, Flavia Bazzoni, Sven Brandau, Nicola Tamassia, Marco A Cassatella, Patrizia Scapini

{"title":"Uncovering common transcriptional features shared by mature peripheral blood PMN-MDSCs and tumor-infiltrating neutrophils in humans.","authors":"Chiara Lattanzi, Francisco Bianchetto-Aguilera, Marta Donini, Francesca Pettinella, Elena Caveggion, Monica Castellucci, Sara Gasperini, Barbara Mariotti, Ilaria Signoretto, Maurizio Cantini, Sara Pilotto, Lorenzo Belluomini, Cristina Tecchio, Flavia Bazzoni, Sven Brandau, Nicola Tamassia, Marco A Cassatella, Patrizia Scapini","doi":"10.1080/2162402X.2025.2521396","DOIUrl":"10.1080/2162402X.2025.2521396","url":null,"abstract":"Human polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) consist of circulating low-density neutrophils (LDNs) characterized by the ability to inhibit T-cell responses. In previous studies, we demonstrated that the mature fraction of PMN-MDSCs (i.e. mPMN-MDSCs) exerts more potent immunosuppressive functions than its immature counterpart. More recently, we defined a specific gene signature of mPMN-MDSCs from cancer patients and G-CSF-treated donors (GDs) by bulk RNA sequencing (RNA-seq) experiments. In this study, by performing single-cell RNA-seq (scRNA-seq) experiments of circulating mPMN-MDSCs from non-small cell lung cancer (NSCLC) patients, we identified a major scRNA-seq cell cluster (arbitrarily named NSCLC c6) specifically displaying immunosuppressive and protumor transcriptomic features. Then, by analyzing publicly available scRNA-seq datasets from human tumor-associated neutrophils (TANs), we uncovered three TAN clusters (arbitrarily named TAN c6-c8) that were found to share with NSCLC c6 several common genes and transcription factor (TF) regulons associated with response to hypoxia, positive regulation of angiogenesis, and metabolic reprogramming. Furthermore, by performing scRNA-seq experiments of GD mPMN-MDSCs, we uncovered four scRNA-seq cell clusters (arbitrarily named GD c4-c7) that were enriched for the same genes and pathways characterizing NSCLC c6 and TAN c6-c8 cells. Altogether, these data uncover that human circulating mPMN-MDSCs and TANs from different cancer types share scRNA-seq cell clusters with transcriptomic similarities, supporting the notion that they might be strictly related.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2521396"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545705","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

An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells. 整体膜组成活性肝素酶增强NK细胞的肿瘤浸润能力。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2024-12-09 DOI: 10.1080/2162402X.2024.2437917

Sofia Liborio-Ramos, Isaac Quiros-Fernandez, Neta Ilan, Soaad Soboh, Malik Farhoud, Ruken Süleymanoglu, Michele Bennek, Sara Calleja-Vara, Martin Müller, Israel Vlodavsky, Angel Cid-Arregui

{"title":"An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells.","authors":"Sofia Liborio-Ramos, Isaac Quiros-Fernandez, Neta Ilan, Soaad Soboh, Malik Farhoud, Ruken Süleymanoglu, Michele Bennek, Sara Calleja-Vara, Martin Müller, Israel Vlodavsky, Angel Cid-Arregui","doi":"10.1080/2162402X.2024.2437917","DOIUrl":"10.1080/2162402X.2024.2437917","url":null,"abstract":"Eradication of cancer cells by the immune system requires extravasation, infiltration and progression of immune cells through the tumor extracellular matrix (ECM). These are also critical determinants for successful adoptive cell immunotherapy of solid tumors. Together with structural proteins, such as collagens and fibronectin, heparan sulfate (HS) proteoglycans are major components of the ECM. Heparanase 1 (HPSE) is the only enzyme known to have endoglycosidase activity that degrades HS. HPSE is expressed at high levels in almost all hematopoietic cells, which suggests that it plays a relevant role in immune cell migration through solid tissues. Besides, tumor cells express also HPSE as a way to facilitate tumor cell resettlement and metastasis. Therefore, an increase in HPSE in the tumor ECM would be detrimental. Here, we analyzed the effects of constitutive expression of an active, membrane-bound HPSE on the ability of human natural killer (NK) cells to infiltrate tumors and eliminate tumor cells. We demonstrate that NK cells expressing a chimeric active form of HPSE on the cell surface as an integral membrane protein, display significantly enhanced infiltration capability into spheroids of various cancer cell lines, as well as into xenograft tumors in immunodeficient mice. As a result, tumor growth was significantly suppressed without causing noticeable side effects. Altogether, our results suggest that a constitutively expressed active HSPE on the surface of immune effector cells enhances their capability to access and eliminate tumor cells. This strategy opens new possibilities for improving adoptive immune treatments using NK cells.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2437917"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802842","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

Assessment of adenosinergic activity of small extracellular vesicles in plasma of cancer patients and healthy donors. 肿瘤患者和健康供体血浆细胞外小泡腺苷能活性的评估。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2024-12-20 DOI: 10.1080/2162402X.2024.2444704

Chang Sook Hong, Elizabeth V Menchikova, Yana Najjar, Theresa L Whiteside, Edwin K Jackson

{"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":"10.1080/2162402X.2024.2444704","url":null,"abstract":"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.","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}

引用次数: 0

Hyperdifferentiated murine melanoma cells promote adaptive anti-tumor immunity but activate the immune checkpoint system. 高分化小鼠黑色素瘤细胞促进适应性抗肿瘤免疫，但激活免疫检查点系统。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2024-12-08 DOI: 10.1080/2162402X.2024.2437211

Yukie Ando, Yutaka Horiuchi, Sara Hatazawa, Momo Mataki, Akihiro Nakamura, Takashi Murakami

{"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":"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, in vivo 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.","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}

引用次数: 0