Oncoimmunology最新文献_第7页

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

Mature tertiary lymphoid structures linked to HPV status and anti-PD-1 based chemoimmunotherapy response in head and neck squamous cell carcinoma. 头颈部鳞状细胞癌中与HPV状态和抗pd -1化学免疫治疗反应相关的成熟三级淋巴结构

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-07-07 DOI: 10.1080/2162402X.2025.2528109

Lizao Zhang, Siqi Ren, Tianjun Lan, Ventin Marco, Niu Liu, Bin Wei, Yunsheng Chen, Jiaying Wu, Qunxing Li, Fan Wu, Peichia Lu, Jiahao Miao, Hsinyu Lin, Xinhui Wang, Jianglong Zhong, Jinsong Li, Song Fan

{"title":"Mature tertiary lymphoid structures linked to HPV status and anti-PD-1 based chemoimmunotherapy response in head and neck squamous cell carcinoma.","authors":"Lizao Zhang, Siqi Ren, Tianjun Lan, Ventin Marco, Niu Liu, Bin Wei, Yunsheng Chen, Jiaying Wu, Qunxing Li, Fan Wu, Peichia Lu, Jiahao Miao, Hsinyu Lin, Xinhui Wang, Jianglong Zhong, Jinsong Li, Song Fan","doi":"10.1080/2162402X.2025.2528109","DOIUrl":"10.1080/2162402X.2025.2528109","url":null,"abstract":"Mature tertiary lymphoid structures (TLSs) are immune aggregates associated with immune checkpoint blockade (ICB) responses in various cancers, yet their role in chemoimmunotherapy response in head and neck squamous cell carcinoma (HNSCC) remains unclear. By analyzing TCGA-HNSC transcriptomic data and pathology slides, we identified an immune subtype enriched in TLSs, predominantly in HPV-positive tumors, which correlated with favorable immunotherapy response. Single-cell and spatial transcriptomics further revealed distinct TLS compositions, with mature TLSs enriched in germinal center B cells, follicular helper T cells, and resident memory CD8 T cells, while immature TLSs contained FCRL4+ B cells and peripheral helper T cells. Multispectral immunohistochemistry, flow cytometry, and ELISA validated these findings. Notably, neoadjuvant chemoimmunotherapy promoted mature TLS formation. These results suggest that TLS maturity correlates with HPV status and response to anti-PD-1-based chemoimmunotherapy, providing insights for potential therapeutic strategies in HNSCC.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2528109"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576642","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 SNP-dependent cancer-testis antigenic epitope serves as a promising immunotherapeutic target for cancer. 一个snp依赖的癌睾丸抗原表位作为一个有希望的癌症免疫治疗靶点。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-07-09 DOI: 10.1080/2162402X.2025.2528110

Kenji Murata, Tomoyuki Minowa, Tomohide Tsukahara, Taku Yoshida, Akiko Minami, Munehide Nakatsugawa, Yuka Mizue, Aiko Murai, Serina Tokita, Kenta Sasaki, Hisashi Uhara, Terufumi Kubo, Takayuki Kanaseki, Toshihiko Torigoe, Yoshihiko Hirohashi

{"title":"An SNP-dependent cancer-testis antigenic epitope serves as a promising immunotherapeutic target for cancer.","authors":"Kenji Murata, Tomoyuki Minowa, Tomohide Tsukahara, Taku Yoshida, Akiko Minami, Munehide Nakatsugawa, Yuka Mizue, Aiko Murai, Serina Tokita, Kenta Sasaki, Hisashi Uhara, Terufumi Kubo, Takayuki Kanaseki, Toshihiko Torigoe, Yoshihiko Hirohashi","doi":"10.1080/2162402X.2025.2528110","DOIUrl":"10.1080/2162402X.2025.2528110","url":null,"abstract":"T cells recognize peptides presented by human leukocyte antigen molecules on the cell surface, enabling the immune surveillance of pathological conditions such as cancer. Cancer-testis (CT) antigens are promising targets for cancer immunotherapy because of their restricted expression in normal tissues. In this study, we performed antigen screening of T cell receptors isolated from tumor-infiltrating lymphocytes (TILs) in acral melanoma, using cDNA expression cloning and identified a novel CT antigenic epitope encoded by MAGE-A6 with a single nucleotide polymorphism (SNP). This SNP conferred immunogenicity to the epitope, eliciting a robust immune response against tumor cells. While antigen identification has increasingly relied on reverse immunology approaches using reference sequences that do not contain SNPs, forward immunology approaches, such as cDNA expression cloning, directly identify antigens recognized by T cells exhibiting immune responses, enabling the detection of SNP-derived epitopes. Furthermore, in hot tumors such as acral melanoma that are characterized by a low tumor mutational burden, but high TIL infiltration, TILs predominantly respond to shared antigens with high immunogenicity. These findings underscore the utility of forward immunology in antigen discovery and highlight the potential of SNP-dependent tumor antigens in cancer immunotherapy.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2528110"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592698","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

CyTOF profiling of bone marrow immune dynamics across myeloma stages. 骨髓免疫动力学在骨髓瘤分期的CyTOF分析。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-08-18 DOI: 10.1080/2162402X.2025.2542333

Dana Cholujova, Gabor Beke, Lubos Klucar, Lubos Drgona, Zuzana Valuskova, Merav Leiba, Efstathios Kastritis, David M Dorfman, Kenneth C Anderson, Jana Jakubikova

{"title":"CyTOF profiling of bone marrow immune dynamics across myeloma stages.","authors":"Dana Cholujova, Gabor Beke, Lubos Klucar, Lubos Drgona, Zuzana Valuskova, Merav Leiba, Efstathios Kastritis, David M Dorfman, Kenneth C Anderson, Jana Jakubikova","doi":"10.1080/2162402X.2025.2542333","DOIUrl":"10.1080/2162402X.2025.2542333","url":null,"abstract":"Multiple myeloma (MM) orchestrates a profound disruption of immune balance within the bone marrow (BM) microenvironment, driving disease progression and therapeutic resistance. To better understand these complex immune dynamics, we used high-dimensional mass cytometry (CyTOF) profiling to comprehensively characterize the immune landscape of the BM across different stages of myeloma progression, including MGUS (n = 16), smoldering MM (SMM; n = 25), and active MM, both newly diagnosed (n = 43) and relapsed/refractory (n = 104). Our analysis revealed substantial immune remodeling during disease progression, characterized by adaptive immune suppression and extensive infiltration of innate immune populations. Transformation from MGUS to SMM was marked by significant alterations in central and effector memory T helper cells, effector cytotoxic T cells, and an enrichment of monocytic and neutrophil subsets. Active MM stages were further distinguished by increased expansion of myeloid and monocytic lineages, alongside a pronounced reduction in progenitor and transitional B cells. Correspondence analysis demonstrated that specific immune profiles were significantly associated with clinical outcomes, including progression-free survival and overall survival. This study highlights the potential of CyTOF-based molecular profiling to unravel the intricate immune dynamics of the BM microenvironment across MM disease stages, enhancing our understanding of MM pathogenesis and providing a foundation for identifying prognostic biomarkers and tailoring precision immunotherapeutic strategies.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2542333"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876219","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

Anti-FAP CAR-NK cells as a novel targeted therapy against cervical cancer and cancer-associated fibroblasts. 抗fap CAR-NK细胞作为一种新的靶向治疗宫颈癌和癌症相关成纤维细胞。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-09-17 DOI: 10.1080/2162402X.2025.2556714

Robert Polten, Ivana Kutle, Jan Lennart Stalp, Jens Hachenberg, Ann-Kathrin Seyda, Lavinia Neubert, Jan C Kamp, Constantin von Kaisenberg, Dirk Schaudien, Peter Hillemanns, Rüdiger Klapdor, Michael Morgan, Axel Schambach

{"title":"Anti-FAP CAR-NK cells as a novel targeted therapy against cervical cancer and cancer-associated fibroblasts.","authors":"Robert Polten, Ivana Kutle, Jan Lennart Stalp, Jens Hachenberg, Ann-Kathrin Seyda, Lavinia Neubert, Jan C Kamp, Constantin von Kaisenberg, Dirk Schaudien, Peter Hillemanns, Rüdiger Klapdor, Michael Morgan, Axel Schambach","doi":"10.1080/2162402X.2025.2556714","DOIUrl":"https://doi.org/10.1080/2162402X.2025.2556714","url":null,"abstract":"The tumor microenvironment (TME) has a central role in many cancers, particularly by fostering an immunosuppressive milieu. Chimeric antigen receptor (CAR)-based immunotherapy displays a promising strategy to re-direct immune cells toward specific antigens, thereby inducing targeted cytotoxicity. The fibroblast activation protein (FAP) is overexpressed in various cancer types and has shown promise in CAR-based therapies. However, its application in gynecological cancers remains unexplored. This study evaluates the efficacy of anti-FAP CAR-NK cells as a targeted immunotherapy for cervical cancer and cancer-associated fibroblasts (CAFs). FAP expression was quantified on cervical cancer cell lines, primary cervical cancer tissues, and cells isolated from these tissues. Alpharetroviral SIN vectors were used to transduce NK-92 cells and primary cord blood-derived NK cells with 3rd-generation anti-FAP CARs. Immunohistochemistry and flow cytometry revealed high FAP expression on CaSki cells, cervical cancer tissues, and primary cervical CAFs. In 2D co-cultures with FAP-positive target cells, anti-FAP CAR-NK cells exhibited significantly enhanced cytotoxicity and elevated degranulation compared to control NK cells, with no observed effects against FAP-negative target cells. Primary NK cells revealed high cytotoxicity against cervical cancer cells with a high release of cytolytic enzymes. Anti-FAP CAR-NK cells also showed efficient elimination of cervical cancer cells and CAFs in 3D tumor spheroid models. These findings underscore the potential of anti-FAP CAR-NK cells as a potent therapeutic approach for cervical cancer and suggest broader applicability in diseases characterized by high FAP expression.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2556714"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076333","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

Divergent on-target off-tumor effects by CAR T and CAR NK cells suggest different efficacy and safety of cell therapies. CAR - T和CAR - NK细胞不同的靶外肿瘤效应表明细胞疗法的疗效和安全性不同。

IF 6.5 2区医学

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-09-05 DOI: 10.1080/2162402X.2025.2546443

Katharina Schindler-Wnek, Anika Stahringer, Nadine Heimer, Ulrike Koehl, Stephan Fricke, Dominik Schmiedel

{"title":"Divergent on-target off-tumor effects by CAR T and CAR NK cells suggest different efficacy and safety of cell therapies.","authors":"Katharina Schindler-Wnek, Anika Stahringer, Nadine Heimer, Ulrike Koehl, Stephan Fricke, Dominik Schmiedel","doi":"10.1080/2162402X.2025.2546443","DOIUrl":"10.1080/2162402X.2025.2546443","url":null,"abstract":"CAR-based cell therapies have shown clinical success in treating various cancers, with CAR T cell therapies entering the clinical route and CAR NK cell therapies being evaluated in early-stage clinical trials. A key challenge is the presence of tumor-associated antigens on healthy cells, risking on-target off-tumor toxicities. Our comparative analysis of CAR T and CAR NK cells targeting the multiple myeloma-associated antigens BCMA, SLAMF7, and CD38 revealed that antigen density on target cells significantly modulates CAR NK cell activation and cytotoxicity. The cytotoxic potential of CAR NK cells was comparable to that of CAR T cells when targeting BCMA and CD38, but notable differences were observed in SLAMF7-directed CAR cells. While CAR sensitivity was similar in both cell types, CAR NK cell activity was balanced by inhibitory receptors like KIRs and NKG2A. This balance allows effective tumor control while potentially reducing on-target off-tumor effects on healthy cells with low antigen expression. Consequently, CAR NK cells offer greater flexibility in target antigen selection, potentially expanding the range of targetable antigens for cancer immunotherapy.","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"14 1","pages":"2546443"},"PeriodicalIF":6.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001706","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