Molecular Oncology最新文献_第4页

KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study. 导管内乳头状黏液性肿瘤患者无细胞DNA和循环上皮细胞中的KRAS和GNAS突变--一项观察性试验研究。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-07-01 Epub Date: 2024-09-01 DOI: 10.1002/1878-0261.13719

Christine Nitschke, Marie Tölle, Philipp Walter, Kira Meißner, Mara Goetz, Jolanthe Kropidlowski, Andreas W Berger, Jakob R Izbicki, Felix Nickel, Thilo Hackert, Klaus Pantel, Harriet Wikman, Faik G Uzunoglu

{"title":"KRAS and GNAS mutations in cell-free DNA and in circulating epithelial cells in patients with intraductal papillary mucinous neoplasms-an observational pilot study.","authors":"Christine Nitschke, Marie Tölle, Philipp Walter, Kira Meißner, Mara Goetz, Jolanthe Kropidlowski, Andreas W Berger, Jakob R Izbicki, Felix Nickel, Thilo Hackert, Klaus Pantel, Harriet Wikman, Faik G Uzunoglu","doi":"10.1002/1878-0261.13719","DOIUrl":"10.1002/1878-0261.13719","url":null,"abstract":"Intraductal papillary mucinous neoplasms (IPMNs) are potential precursor lesions of pancreatic cancer. We assessed the efficacy of screening for KRAS proto-oncogene, GTPase (KRAS), and GNAS complex locus (GNAS) mutations in cell-free DNA (cfDNA)-using digital droplet polymerase chain reaction (ddPCR) and circulating epithelial cell (CEC) detection-as biomarkers for risk stratification in IPMN patients. We prospectively collected plasma samples from 25 resected patients at risk of malignant progression, and 23 under clinical surveillance. Our findings revealed KRAS mutations in 10.4% and GNAS mutations in 18.8% of the overall cohort. Among resected IPMN patients, KRAS and GNAS mutation detection rates were 16.0% and 32.0%, respectively, whereas both rates were 4.0% in conservatively managed IPMN. GNAS mutations in cfDNA were significantly more prevalent in resected IPMN (P = 0.024) compared with IPMN under surveillance. No CECs were detected. The absence of KRAS and GNAS mutations could be a reliable marker for branch duct IPMN without worrisome features. The emergence of GNAS mutations could prompt enhanced imaging surveillance. Neither the presence of established worrisome features nor GNAS or KRAS mutations appear effective in identifying high-grade dysplasia among IPMN patients.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2144-2153"},"PeriodicalIF":6.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109590","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

Machine learning for identifying liver and pancreas cancers through comprehensive serum glycopeptide spectra analysis: a case-control study. 通过综合血清糖肽谱分析识别肝癌和胰腺癌的机器学习：一项病例对照研究。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-30 DOI: 10.1002/1878-0261.70084

Motoyuki Kohjima, Yuko Takami, Ken Kawabe, Kazuhiro Tanabe, Chihiro Hayashi, Mikio Mikami, Tetsuya Kusumoto

{"title":"Machine learning for identifying liver and pancreas cancers through comprehensive serum glycopeptide spectra analysis: a case-control study.","authors":"Motoyuki Kohjima, Yuko Takami, Ken Kawabe, Kazuhiro Tanabe, Chihiro Hayashi, Mikio Mikami, Tetsuya Kusumoto","doi":"10.1002/1878-0261.70084","DOIUrl":"https://doi.org/10.1002/1878-0261.70084","url":null,"abstract":"Liver and pancreatic cancers are difficult to detect early, leading to high mortality rates. Blood-based diagnostics present a viable alternative for earlier detection, potentially improving survival rates. The comprehensive serum glycopeptide spectra analysis (CSGSA) method combines enriched glycopeptides (EGPs) with conventional tumor markers through machine learning to accurately identify early stage cancers. Here, we analyzed nine tumor markers (CA19-9, AFP, PSA, CEA, CA125, CYFRA, CA15-3, SCC antigen, and NCC-ST439) in 119 patients with pancreatic cancer and 49 with hepatocellular carcinoma, alongside 590 healthy controls. We also analyzed EGPs using liquid chromatography-mass spectrometry. We found that α1-antitrypsin with a fully sialylated biantennary glycan at asparagine 271 and α2-macroglobulin with a fully sialylated biantennary glycan at asparagine 70 effectively distinguished liver and pancreatic cancers. The integration of these two glycopeptides, along with the nine tumor markers and 1688 EGPs using a machine learning model enhanced diagnostic accuracy, achieving a receiver operating characteristic-area under curve (ROC-AUC) score of 0.996. CSGSA has the potential to minimize the need for invasive diagnostic procedures and serves as a promising tool for widespread screening.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528835","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

Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals. 高剂量放射性碘治疗与老年人ppm1d突变克隆造血的关系

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-26 DOI: 10.1002/1878-0261.70078

Jaeryuk Kim, Sungwoo Bae, Jaeyong Choi, Sun-Wha Im, Bukyoung Cha, Gyeongseo Jung, Sun Wook Cho, Eul-Ju Seo, Young Ah Lee, Jin Chul Paeng, Young Joo Park, Jong-Il Kim

{"title":"Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals.","authors":"Jaeryuk Kim, Sungwoo Bae, Jaeyong Choi, Sun-Wha Im, Bukyoung Cha, Gyeongseo Jung, Sun Wook Cho, Eul-Ju Seo, Young Ah Lee, Jin Chul Paeng, Young Joo Park, Jong-Il Kim","doi":"10.1002/1878-0261.70078","DOIUrl":"https://doi.org/10.1002/1878-0261.70078","url":null,"abstract":"While radioactive iodine therapy (RAIT) has been an effective treatment for thyroid cancer, its link to clonal hematopoiesis (CH) has been yet underexplored. In this study, error-corrected sequencing (median depth: 1926×) of 93 CH-related genes was performed from the blood samples of 358 thyroid cancer patients, including 110 controls (no RAIT) and 248 RAIT recipients. RAIT recipients were stratified into low- and high-dose groups using a 7.4 GBq cutoff. Multivariable logistic regression revealed that the high-dose group had a higher CH prevalence with variant allele frequency (VAF) higher than 2% compared to controls, especially in patients aged ≥50 (OR = 2.44, CI = 1.04-6.00, P = 0.04). Thirteen genes had mutations with VAF >2%, with DNMT3A, TET2, and PPM1D being the most common. Notably, only the PPM1D mutations were significantly linked to RAIT, occurring more frequently in the high-dose group (13%) compared to the low-dose group (5%) or controls (2%) at a VAF cutoff of 0.5%. In silico analyses indicated that truncating PPM1D mutations confer a selective advantage under high-dose RAIT and with older age. Although the prognostic implications of PPM1D-mutated CH remain to be further elucidated, these findings offer valuable insights for optimizing RAIT dosing in thyroid cancer patients.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506842","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

Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma. 靶向碳酸酐酶IX/XII可阻止基质乳酸在前列腺癌中的抗铁沉降作用。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-26 DOI: 10.1002/1878-0261.70083

Elisa Pardella, Giuseppina Comito, Luigi Ippolito, Erica Pranzini, Marta Iozzo, Giulia Gangarossa, Francesca Virgilio, Silvia Bua, Alessio Nocentini, Giada Sandrini, Nicla Lorito, Marina Bacci, Gabriella Nesi, Pietro Spatafora, Sergio Serni, Claudiu T Supuran, Andrea Morandi, Paola Chiarugi, Elisa Giannoni

{"title":"Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.","authors":"Elisa Pardella, Giuseppina Comito, Luigi Ippolito, Erica Pranzini, Marta Iozzo, Giulia Gangarossa, Francesca Virgilio, Silvia Bua, Alessio Nocentini, Giada Sandrini, Nicla Lorito, Marina Bacci, Gabriella Nesi, Pietro Spatafora, Sergio Serni, Claudiu T Supuran, Andrea Morandi, Paola Chiarugi, Elisa Giannoni","doi":"10.1002/1878-0261.70083","DOIUrl":"https://doi.org/10.1002/1878-0261.70083","url":null,"abstract":"Ferroptosis is a form of regulated cell death dependent on iron-driven phospholipid peroxidation and is controlled by both cell autonomous and non-cell autonomous mechanisms. In prostate cancer (PCa), tumor cells engage in a metabolic crosstalk with cancer-associated fibroblasts (CAFs), resulting in increased utilization of CAF-secreted lactic acid, that ultimately supports cancer aggressiveness. In this context, the effect of the prostate tumor microenvironment in modulating ferroptosis sensitivity has not yet been extensively investigated. Here, we demonstrate that CAF-secreted lactic acid protects PCa cells from ferroptosis induction and supports the upregulation of the antioxidant enzyme glutathione peroxidase 4 (GPX4). Interestingly, targeting carbonic anhydrase IX/XII (CA IX/XII), the main regulators of microenvironmental acidosis, in tumor and stromal compartments hinders lactic acid shuttle within the tumor-stroma interplay and thus, prevents ferroptosis resistance induced by lactic acid. Analyses of tissue samples from PCa patients also revealed that GPX4, CA IX, and CA XII expression levels increase during PCa progression. Overall, these findings support a role for stromal lactic acid in mediating ferroptosis resistance in PCa, identifying CA IX/XII as potential therapeutic targets regulating ferroptosis sensitivity.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506843","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

Small modifier, big decision: switching to SUMO mode adds weight to cancer stemness in mammary tumors. 小的修改，大的决定：切换到SUMO模式增加了乳腺肿瘤的癌性。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-23 DOI: 10.1002/1878-0261.70082

Veronika Yevdokimova, Yannick D Benoit

引用次数: 0

Integrative miRNOMe profiling reveals the miR-195-5p-CHEK1 axis and its impact on luminal breast cancer outcomes. 综合miRNOMe分析揭示了miR-195-5p-CHEK1轴及其对腔内乳腺癌结局的影响。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-23 DOI: 10.1002/1878-0261.70077

Veronika Boušková, Marie Ehrlichová, Alžběta Spálenková, Ivona Krus, Simona Šůsová, Viktor Hlaváč, Vlasta Němcová, Renata Koževnikovová, Markéta Trnková, David Vrána, Jiří Gatěk, Kateřina Kopečková, Marcela Mrhalová, Soňa Měšťáková, Pavel Souček

{"title":"Integrative miRNOMe profiling reveals the miR-195-5p-CHEK1 axis and its impact on luminal breast cancer outcomes.","authors":"Veronika Boušková, Marie Ehrlichová, Alžběta Spálenková, Ivona Krus, Simona Šůsová, Viktor Hlaváč, Vlasta Němcová, Renata Koževnikovová, Markéta Trnková, David Vrána, Jiří Gatěk, Kateřina Kopečková, Marcela Mrhalová, Soňa Měšťáková, Pavel Souček","doi":"10.1002/1878-0261.70077","DOIUrl":"https://doi.org/10.1002/1878-0261.70077","url":null,"abstract":"The luminal subtype (estrogen receptor-positive, ER+) is the most common and the most heterogeneous type of breast carcinoma (BC) in women. During our study, we determined expression levels of all microRNAs (miRNome) in 101 ER+ BC samples and identified 25 miRNAs being associated with proliferative markers. Using comprehensive in silico analyses we prioritized CHEK1, CDC25A, and CCNE1 as candidate genes affecting the proliferation of ER+ BC, with two microRNAs from the miR-497∼195 cluster identified as their potential regulators. In a cohort of 217 patients, we found a significant association between high expression of CHEK1 and shorter relapse-free survival (RFS) in luminal BC patients treated with adjuvant chemotherapy, especially in patients with luminal A subtype. In patients treated with neoadjuvant therapy, the opposite role for RFS was observed for hsa-miR-195-5p. Subsequently, we confirmed the potency of hsa-miR-195-5p to inhibit the expression of CHEK1 in vitro. Moreover, the specific Chk1 inhibitor rabusertib (LY2603618) significantly enhanced the efficacy of doxorubicin in both ER+ and ER- cell lines. In summary, we have identified the association of a specific miRNA profile with highly proliferative luminal BCs and demonstrated the ability of hsa-miR-195-5p to inhibit CHEK1 expression in BC in vitro, underlining the importance of CHEK1 expression and its inhibition for prognosis and treatment of patients with luminal BCs.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476055","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

Chimeric diphtheria toxin-CCL8 cytotoxic peptide for breast cancer management. 嵌合白喉毒素- ccl8细胞毒性肽用于乳腺癌治疗。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-22 DOI: 10.1002/1878-0261.70079

Bernardo Chavez, Asieh Naderi, Kim-Tuyen Huynh-Dam, Vitali Sikirzhytski, Ioulia Chatzistamou, Hippokratis Kiaris

{"title":"Chimeric diphtheria toxin-CCL8 cytotoxic peptide for breast cancer management.","authors":"Bernardo Chavez, Asieh Naderi, Kim-Tuyen Huynh-Dam, Vitali Sikirzhytski, Ioulia Chatzistamou, Hippokratis Kiaris","doi":"10.1002/1878-0261.70079","DOIUrl":"10.1002/1878-0261.70079","url":null,"abstract":"Deregulation of chemokine CCL8 expression is common in various malignancies and other pathologies and plays a causative role in disease progression. However, despite CCL8's acknowledged role in pathology, inhibition of its activity does not represent a strategy of choice for cancer management. This is because its function overlaps with that of the other structurally related chemokines, and its activity is mediated by more than one receptor. To overcome this limitation, we hypothesized that ablation of CCL8 cellular targets, as opposed to disruption of CCL8 activity, may be more advantageous. Therefore, we developed DTCCL8, a chimeric cytotoxic peptide that delivers diphtheria toxin into cells expressing CCL8 receptors which are overexpressed in both the cells of tumor microenvironment and the cancer cells. The specificity of this peptide was confirmed in vitro by testing the cytotoxic activity of breast cancer cells overexpressing CCR5, a major CCL8 receptor, and by a neutralizing anti-CCL8 antibody we developed. In vivo, DTCCL8 transiently reduced lymphocytes in blood, and its anticancer activity was confirmed in mouse breast cancers triggered by the polyoma middle T oncogene. These findings suggest that DTCCL8 can be used as a prototype for the development of a novel class of breast cancer therapeutics, targeting chemokine targets instead of inhibiting their activity. These cytotoxic peptides may also be useful for managing cancers and other immune system-associated pathologies.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369075","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

EMT-associated bias in the Parsortix® system observed with pancreatic cancer cell lines. Parsortix®系统在胰腺癌细胞系中观察到emt相关偏倚

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-18 DOI: 10.1002/1878-0261.70066

Nele Vandenbussche, Renske Imschoot, Béatrice Lintermans, Lode Denolf, Joachim Taminau, Charlotte Fieuws, Geert Berx, Kris Gevaert, Kathleen B M Claes

{"title":"EMT-associated bias in the Parsortix® system observed with pancreatic cancer cell lines.","authors":"Nele Vandenbussche, Renske Imschoot, Béatrice Lintermans, Lode Denolf, Joachim Taminau, Charlotte Fieuws, Geert Berx, Kris Gevaert, Kathleen B M Claes","doi":"10.1002/1878-0261.70066","DOIUrl":"https://doi.org/10.1002/1878-0261.70066","url":null,"abstract":"Pancreatic cancer has a 5-year survival rate of 12%, highlighting the need for reliable biomarkers for early detection and disease monitoring. Circulating tumor cells (CTCs) have emerged as a promising biomarker, yet their detection remains challenging. This study evaluates the Parsortix® system, a microfluidic device that enriches CTCs based on size and deformability, using pancreatic cancer cell lines. As increasing evidence indicates that during epithelial-to-mesenchymal transition (EMT) a cell's deformability increases, we evaluated possible biases by the device. The EMT stage of three pancreatic cancer cell lines, CAPAN-1, MIA PaCa-2, and PANC-1, was assessed to classify them as epithelial, mesenchymal-like, and hybrid, respectively. Spike-in experiments showed that epithelial and hybrid phenotypes were more efficiently captured (62.6 ± 18.5% and 65.4 ± 11.1%) than mesenchymal-like cancer cells (32.8 ± 10.2%). These results were confirmed using an EMT-inducible breast cancer cell line. Lower recovery rates were found for the cells in a mesenchymal-like state (31.5 ± 6.4%) than those in an epithelial state (47.56 ± 7.2%). In conclusion, the Parsortix® device may underestimate the number of mesenchymal CTCs.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326225","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

Evaluation and modification of tumor cell isolation techniques from malignant effusions for rapid drug sensitivity testing. 用于快速药敏试验的恶性积液肿瘤细胞分离技术的评价与改进。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-17 DOI: 10.1002/1878-0261.70072

Navit Mooshayef, Hana Barhom, Sumit Chatterji, Netta Hecht, Oran Warhaftig, Iris Kamer, Oranit Zadok, Jair Bar, Limor Broday, Amir Onn, Michael Peled

{"title":"Evaluation and modification of tumor cell isolation techniques from malignant effusions for rapid drug sensitivity testing.","authors":"Navit Mooshayef, Hana Barhom, Sumit Chatterji, Netta Hecht, Oran Warhaftig, Iris Kamer, Oranit Zadok, Jair Bar, Limor Broday, Amir Onn, Michael Peled","doi":"10.1002/1878-0261.70072","DOIUrl":"https://doi.org/10.1002/1878-0261.70072","url":null,"abstract":"Non-small cell lung cancer treatment decisions rely on several diagnostic steps. Tests that rely on DNA sequencing often fail to capture the full mutational landscape of tumor cells, and drug sensitivity testing (DST) has limitations hindering widespread use currently. One of the major challenges for DST is the rapid isolation of a sufficient number of live tumor cells that would allow testing of multiple drugs simultaneously. To address this challenge, we have developed a DST procedure specifically tailored for tumor cells originating from malignant pleural effusions. We first identified tumor cells by anti-epithelial cell adhesion molecule (EpCAM) flow cytometry and then compared several methods for tumor cell isolation: immunomagnetic enrichment of epithelial cells using EpCAM, negative selection via immunomagnetic CD45+ cell depletion, and size-based separation and capture of tumor cells utilizing cell strainers. Of these methods, repeated rounds of CD45+ cell depletion, in which the number of rounds is set by the initial percentage of tumor cells in the sample, were the most effective. By combining tumor cell enrichment with DST, we have developed a system which generates DST results that correlate with clinical outcomes.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310214","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

Beyond cytotoxic T cells: reprogrammed regulatory T cells help facilitate response to dual checkpoint blockade. 超越细胞毒性T细胞：重编程调节性T细胞有助于促进对双检查点封锁的反应。

IF 6.6 2区医学

Molecular Oncology Pub Date : 2025-06-15 DOI: 10.1002/1878-0261.70076

Tullia C Bruno, Anthony R Cillo

{"title":"Beyond cytotoxic T cells: reprogrammed regulatory T cells help facilitate response to dual checkpoint blockade.","authors":"Tullia C Bruno, Anthony R Cillo","doi":"10.1002/1878-0261.70076","DOIUrl":"https://doi.org/10.1002/1878-0261.70076","url":null,"abstract":"Combination immunotherapies have entered the treatment armamentarium of oncology, but important knowledge gaps remain in our understanding of how these therapeutics work. A recent study by Rolig, Peng, and colleagues has shed new light on how dual blockade of PD1 and LAG3 enhances antitumor immunity. The authors first interrogated LAG3 expression on T cells across murine tumor models, classifying the models as LAG3hi or LAG3lo. Next, they found that LAG3hi models were unresponsive to anti-PD1 alone but responsive to combination therapy with anti-PD1 + anti-LAG3. Surprisingly, the response to anti-PD1 + anti-LAG3 in LAG3hi models was associated with reprogramming of CD4+ regulatory T cells (Treg) from the canonically immunosuppressive state to an inflammatory state characterized by loss of expression of the transcription factor Foxp3 and upregulation of transcription factor Tbet. Importantly, an analogous reprogrammed Treg state was associated with response to anti-PD1 + anti-LAG3 and longer overall survival in patients with metastatic melanoma. This work highlights the importance of cells beyond cytotoxic CD8+ T cells as drivers of response to immunotherapy and sets the stage for subsequent mechanistic and translational studies.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302516","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