British Journal of Cancer最新文献

{"title":"Sequential ATR and PARP inhibition overcomes acquired DNA damaging agent resistance in pancreatic ductal adenocarcinoma.","authors":"Katharine J Herbert, Rosie Upstill-Goddard, Stephan B Dreyer, Selma Rebus, Christian Pilarsky, Mukhopadhyay Debabrata, Christopher J Lord, Andrew V Biankin, Fieke E M Froeling, David K Chang","doi":"10.1038/s41416-025-03051-z","DOIUrl":"https://doi.org/10.1038/s41416-025-03051-z","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal cancer. While DNA damaging agents such as platinum and PARP inhibitors have derived clinical benefits, acquired resistance invariably develops. Hence there is an urgent need for novel therapeutic strategies to overcome acquired resistance.</p><p><strong>Methods: </strong>Clinically relevant resistance in PDAC patient-derived cell lines was achieved by extended exposure to chemotherapy agents. Synergy scoring, clonogenicity, flow cytometry, immunofluorescence, and transcriptomic analysis were used to investigate the efficacy of ATR (ceralasertib) and PARP (olaparib) inhibitors in overcoming acquired resistance.</p><p><strong>Results: </strong>Acquired resistance was associated with transcriptomic shifts in cell cycle checkpoint regulation, metabolic control, DNA damage response (DDR), programmed cell death, and the replication stress response. Combination treatment with ceralasertib, and olaparib was synergistic in all models of acquired resistance. Sequential use of ceralasertib prior to olaparib was highly effective at low dose for DDR proficient models, whereas DDR deficient models responded better with olaparib treatment first.</p><p><strong>Conclusions: </strong>We provide in vitro evidence of a novel therapeutic strategy to overcome acquired resistance to PARP inhibitor and platinum in PDAC, using sequential exposure to ceralasertib and olaparib. A sequential regimen should be investigated clinically to circumvent dose limiting toxicity seen in concurrent combinations.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyst fluid ctDNA as a biomarker for genetic profiling and treatment monitoring in cystic brain metastases.","authors":"Zhen Zhang, Xingyu Jin, Qiang Yin, Peng Li, Zengfeng Sun, Wenliang Li, Qun Liu, Xiaohui Zhang, Peng Wang, Yingzhe Piao, Yalin Lu, Lianwang Li, Kaikai Yi, Chunhua She, Li Ma, Jiangyan Zhang, Xun Jin, Manqing Cao, Xiaoguang Wang","doi":"10.1038/s41416-025-03047-9","DOIUrl":"https://doi.org/10.1038/s41416-025-03047-9","url":null,"abstract":"<p><strong>Background: </strong>Cystic brain metastases (CBM) present significant clinical challenges due to their heterogeneity and the limitations of current diagnostic methods in guiding treatment. Traditional tissue biopsies are invasive and may not capture tumour heterogeneity, while plasma circulating tumour DNA (ctDNA) analysis is impeded by the blood-brain barrier, leading to low sensitivity for detecting intracranial lesions. These limitations create a critical gap in the personalised management of patients with CBM.</p><p><strong>Methods: </strong>We evaluated the utility of cyst fluid ctDNA as a minimally invasive biomarker for genetic profiling and treatment monitoring in CBM patients. ctDNA was extracted from cyst fluid, tumour tissue, plasma, and cerebrospinal fluid (CSF) samples collected from 18 patients. NGS was performed to analyse genetic mutations. Mutation detection rates and genetic heterogeneity were compared across different sample types. Dynamic changes in ctDNA mutation abundance in cyst fluid were assessed in relation to treatment responses.</p><p><strong>Results: </strong>Cyst fluid ctDNA demonstrated a higher mutation detection rate and captured more significant genetic heterogeneity than plasma ctDNA and, in some cases, even matched tissue samples. Clinically significant mutations, including actionable driver genes such as EGFR and TP53, were identified in cyst fluid ctDNA but were undetectable in plasma. Moreover, dynamic changes in the abundance of ctDNA mutations in cyst fluid correlated with treatment responses, indicating its potential for real-time therapeutic efficacy monitoring.</p><p><strong>Conclusions: </strong>Cyst fluid ctDNA provides a sensitive and comprehensive method for capturing the genetic landscape of CBM, effectively overcoming the limitations of tissue biopsies and plasma ctDNA analysis. By establishing a real-time molecular surveillance network, cyst fluid ctDNA analysis redefines precision neuro-oncology paradigms, transitioning CBM management from static histomolecular snapshots to adaptive therapeutic ecosystems.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An FDA-approved drug library screening identifies proteasome inhibitors as selective cytotoxic agents for angiosarcoma cells.","authors":"Che-Yuan Hsu, Teruki Yanagi, Kodai Miyamoto, Satoko Otsuguro, Katsumi Maenaka, Hiroshi Nishihara, Hideki Nakamura, Kenzo Takahashi, Hideyuki Ujiie","doi":"10.1038/s41416-025-03016-2","DOIUrl":"https://doi.org/10.1038/s41416-025-03016-2","url":null,"abstract":"<p><p>Cutaneous angiosarcoma (CAS) is a life-threatening neoplasm with a 5-year survival rate of under 40% in advanced cases. As available treatments for CAS are limited, novel therapeutics must be explored. To identify potential therapeutic candidates, we conducted a drug screening analysis using an angiosarcoma cell line, HAMON. Cancer-related gene analysis revealed alterations in FGFR4, MYCN, CDKN2A, NF1, TP53, KDM6A, ATRX, MSH6, ATM, and NOTCH1 in HAMON cells. Screening of 4681 FDA-approved drugs identified four candidate compounds, with the proteasome inhibitor bortezomib selected for further study. ATP and MTT assays revealed bortezomib to be the most effective candidate against HAMON cells. Clonogenic assays revealed fewer HAMON cell colonies in the range of 1-10 nM bortezomib. DNA-content fluorescence-activated cell sorting analysis revealed a notable increase in the sub-G0/G1 phases, suggesting cell death without cell cycle arrest. Annexin V-propidium iodide staining revealed a significant increase in the percentage of early and late apoptotic cells in the bortezomib group. Mechanistically, bortezomib induced activation of NF-κB and endoplasmic reticulum stress signaling. The administration of bortezomib to immunocompromised mice implanted with HAMON cells induced apoptosis of tumor cells. This study identified the proteasome inhibitor bortezomib as a potential candidate for angiosarcoma in vitro and in vivo.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD49a⁺ NK cells promote esophageal cancer development by inducing MDCSs infiltration via GM-CSF.","authors":"Kele Cui, Shouxin Hu, Yanfang Zha, Keshuo Ding, Haiming Wei, Min Cheng, Xinyu Mei","doi":"10.1038/s41416-025-03065-7","DOIUrl":"https://doi.org/10.1038/s41416-025-03065-7","url":null,"abstract":"<p><strong>Background: </strong>Although extensive evidence indicates that tissue-resident natural killer (trNK) cells are closely related to the development and clinical outcomes of various tumours, their roles in esophageal cancer remain obscure.</p><p><strong>Methods: </strong>Tumour tissues collected from 54 esophageal squamous cell carcinoma (ESCC) patients during surgery and human ESCC tissue arrays including samples from 258 patients were subjected to analyse the phenotype and functions of immune cells.</p><p><strong>Results: </strong>We observed a population of CD49a⁺ NK cells with a CD103^hiCD69^hi resident phenotype predominantly within the CD56^bright NK cell subset in the intratumoral tissue of ESCC patients. These CD49a⁺ trNK cells, characterised by high expression of inhibitory receptors (TIM-3, CD244, TIGIT, PD-1), reduced cytotoxic potential (lower CD16, granzyme B, and perforin), and elevated secretion of IFN-γ and TGF-β, exhibited an exhausted and regulatory phenotype. Their presence was associated with poor prognosis in early-stage ESCC, but not in advanced stages. Mechanistically, these cells were found to enhance the immunosuppressive tumour environment by increasing MDSCs through GM-CSF secretion, thereby facilitating tumour progression.</p><p><strong>Conclusions: </strong>Our research reveals that tumour-infiltrated CD49a⁺ NK cells exhibit exhausted and regulatory profile, capable of inducing the accumulation of MDSCs by secreting GM-CSF, and predict poor clinical outcomes in early-stage ESCC patients. trNK cells in esophageal tissues exhibit antitumor potential via degranulation-mediated elimination of cancer cells, thereby performing immune surveillance. However, during tumour progression, upregulation of immune checkpoint molecules (e.g., TIM3 and CD244) on trNK cells results in reduced cytotoxic activity and an exhausted phenotype. Exhausted trNK cells further enhance the immunosuppressive tumour microenvironment by promoting MDSCs accumulation through GM-CSF secretion, ultimately facilitating tumour progression. The graph was created with BioRender.com.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remodelling hypoxic TNBC microenvironment restores antitumor efficacy of Vγ9Vδ2 T cell therapy.","authors":"Yanyun Jing, Yangzhe Wu, Qinglin Hu, Wenfeng Wu, Dang Li, Wenhao Hu, Heming Li, Minggang Fu, Xin Huang, Yi Hu","doi":"10.1038/s41416-025-03045-x","DOIUrl":"https://doi.org/10.1038/s41416-025-03045-x","url":null,"abstract":"<p><strong>Background: </strong>γδ T cells have emerged as pivotal regulators within the breast cancer tumour microenvironment (TME) and represent a promising therapeutic strategy for late-stage and metastatic breast cancer. In recent years, our research has focused on leveraging allogeneic Vγ9Vδ2 T cells as a novel approach to treat advanced cancers, including triple-negative breast cancer (TNBC). However, the varying clinical outcomes of this therapy have prompted us to investigate the diverse roles of γδ T cells within the TNBC microenvironment and to explore strategies for enhancing therapeutic efficacy through microenvironmental remodelling.</p><p><strong>Methods: </strong>Data from TCGA, publicly available scRNA-seq datasets and a series of experiments including flow cytometry, atomic force microscopy, confocal laser scanning microscopy, mouse model and others were applied to examine the functional heterogeneity of γδ T cells in TNBC, non-TNBC, and healthy individuals.</p><p><strong>Results: </strong>γδ T cells serve as predictive markers of better prognosis in breast cancer. In TNBC tumours, γδ T cells exhibited heightened expression of genes linked to both effector and inhibitory molecules, alongside a significant upregulation of glycolytic activity-patterns not observed in non-TNBC or normal breast tissues. Further analysis demonstrated that hypoxic conditions in the TNBC microenvironment likely contribute to these metabolic changes, leading to upregulation of inhibitory checkpoints and downregulation of effector functions in γδ T cells. Importantly, we showed that suppressing HIF-1 signalling using PX478 enhanced the antitumor efficacy of Vδ2⁺γδ T cell therapy in TNBC-bearing mice.</p><p><strong>Discussion: </strong>This work underscores that remodelling the hypoxic TNBC microenvironment can restore the antitumor activity of Vγ9Vδ2 T cell therapy. Our findings offer a compelling new adjuvant strategy to improve the outcomes of Vγ9Vδ2 T cell-based therapies for advanced breast cancer treatment.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term clinical outcome of patients with metastatic melanoma and initial stable disease during anti-PD-1 checkpoint inhibitor immunotherapy with pembrolizumab.","authors":"Inge Mansfield Noringriis, Marco Donia, Kasper Madsen, Henrik Schmidt, Charlotte Aaquist Haslund, Lars Bastholt, Inge Marie Svane, Eva Ellebaek","doi":"10.1038/s41416-025-03048-8","DOIUrl":"https://doi.org/10.1038/s41416-025-03048-8","url":null,"abstract":"<p><strong>Background: </strong>A substantial number of patients with metastatic melanoma (MM) treated with anti-PD-1 monotherapy have initial stable disease (SD), yet the real-world prognosis of these patients remains unclear.</p><p><strong>Methods: </strong>In this nationwide cohort study, we analysed real-world outcomes of patients with MM treated with pembrolizumab in Denmark. Focusing on patients with initial SD, we assessed best overall response (BOR), progression-free survival (PFS), and overall survival (OS) and identified predictors of survival in multivariable analyses.</p><p><strong>Results: </strong>Out of 1048 included patients, 233 (22.2%) had initial SD with a median PFS and OS of 14.7 and 50.1 months. Subsequent partial response (PR) or complete response (CR) was developed by 44 (18.9%) and 52 (22.3%) patients showing significantly improved PFS compared to patients with continued SD (PR: HR 0.52, 95% CI 0.34-0.81, p = 0.003; CR: HR 0.15, 95% CI 0.07-0.32, p < 0.001) and survival rates comparable to patients with initial PR and CR, respectively. Furthermore, 49 (21.0%) patients showed continued disease control (median follow-up of 82.3 months). For 51.0% of these patients, the last dose of pembrolizumab was administered during SD with a median treatment duration of 12.4 months.</p><p><strong>Conclusions: </strong>Of patients with initial SD, 40% developed a subsequent objective response with improved long-term prognosis comparable to patients with initial response. More than 20% exhibited continued disease control.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of DNA damage response signals and oxidative stress status with nivolumab efficacy in patients with Head and Neck Squamous Cell Carcinoma.","authors":"Christina Papanikolaou, Panagiota Economopoulou, Aris Spathis, Ioannis Kotsantis, Niki Gavrielatou, Maria Anastasiou, Myrto Moutafi, Anastasios Kyriazoglou, George-Romanos P Foukas, Ioannis M Lelegiannis, David Rimm, Ioannis Panayiotides, Periklis Foukas, Vassilis L Souliotis, Amanda Psyrri","doi":"10.1038/s41416-025-03032-2","DOIUrl":"https://doi.org/10.1038/s41416-025-03032-2","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence suggests that deregulation of DNA damage response (DDR) network affects multiple aspects of the immune system. Herein, we tested the hypothesis that DDR-related signals, measured in peripheral blood mononuclear cells (PBMCs) from Head and Neck Squamous Cell Carcinoma (HNSCC) patients, correlate with the response to immune checkpoint inhibitors.</p><p><strong>Methods: </strong>Oxidative stress and DDR-related signals were evaluated in PBMCs from 26 healthy controls and 50 recurrent/metastatic HNSCC patients at baseline, who participated in a phase II nivolumab trial (NCT03652142). Spatial transcriptomics in three molecularly defined tissue compartments (tumour, leucocyte, macrophage) from biopsies of overlapping cases were also investigated.</p><p><strong>Results: </strong>PBMCs from responders to nivolumab therapy showed significantly lower oxidative stress, endogenous DNA damage, DNA repair capacities and apoptosis rates compared with non-responders (all P < 0.04). The analysis of tissue RNA in situ data illustrated that DNA repair pathways showed enrichment in the macrophage compartment of baseline tissue biopsies of responders compared with non-responders (P = 0.049).</p><p><strong>Conclusions: </strong>Our findings demonstrate that oxidative stress and deregulated DDR-related signals measured in PBMCs from HNSCC patients at baseline correlate with response to nivolumab and, if further validated, may be exploited as novel non-invasive biomarkers and the design of clinical trials.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer.","authors":"Keun Wook Lee, Da Young Zang, Hyung-Don Kim, Jin-Won Kim, Bum Jun Kim, Yoon-Koo Kang, Min-Hee Ryu, Hark Kyun Kim","doi":"10.1038/s41416-025-03052-y","DOIUrl":"https://doi.org/10.1038/s41416-025-03052-y","url":null,"abstract":"<p><strong>Background: </strong>This multicenter phase Ib/II trial aimed to evaluate the safety and efficacy of combining durvalumab, tremelimumab, and paclitaxel as second-line treatment for biomarker-selected patients with metastatic gastric cancer.</p><p><strong>Methods: </strong>In phase Ib, the standard 3 + 3 dose escalation method was used. Durvalumab and tremelimumab were administered every 4 weeks for 13 and 4 cycles, respectively, combining paclitaxel 80 mg/m² (dose level 2) or 60 mg/m² (dose level 1) on days 1, 8, and 15. The primary outcome for phase II was the objective response rate (ORR).</p><p><strong>Results: </strong>In phase Ib (n = 7), dose level-1 was selected as the recommended phase II dose. In phase II, 48 patients were enrolled: microsatellite instability-high or deficient mismatch repair protein tumors (n = 16); EBV-positive tumors (n = 15); high tumor mutation burden ( ≥ 5/Mb) (n = 11); CD274 amplification (n = 5); and POLD1 mutation (n = 1). The ORR was 52.1%, meeting the primary endpoint. The median progression-free survival and overall survival were 5.3 and 13.1 months, respectively. The most common any-grade and grade 3-4 adverse events were anemia (41.7%) and neutropenia (10.4%), respectively.</p><p><strong>Conclusions: </strong>Durvalumab-tremelimumab with paclitaxel was tolerable and efficacious in biomarker-selected gastric cancer patients as a second-line treatment, highlighting the importance of biomarker-based approaches for immunotherapy in gastric cancer.</p><p><strong>Clinical trial registration: </strong>NCT03751761.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometric insights into the protein composition of human cutaneous neurofibromas: comparison of neurofibromas with the overlying skin.","authors":"Roope A Kallionpää, Eija Martikkala, Pekka Haapaniemi, Sanna-Maria Karppinen, Pilvi Riihilä, Anne Rokka, Ilmo Leivo, Taina Pihlajaniemi, Sirkku Peltonen, Juha Peltonen","doi":"10.1038/s41416-025-03055-9","DOIUrl":"https://doi.org/10.1038/s41416-025-03055-9","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous neurofibromas (cNFs) are the hallmark of the tumor-predisposition syndrome neurofibromatosis 1 (NF1). While cNFs are always benign, they markedly decrease quality of life in individuals with NF1. Understanding the differences between cNFs and the skin is essential for developing treatments for cNFs.</p><p><strong>Methods: </strong>We collected 15 cNFs from four NF1 individuals and used mass spectrometry to compare the tumor tissue with the skin overlying each tumor. Data were analyzed based on Gene Ontology (GO) terms.</p><p><strong>Results: </strong>The expression patterns of the Schwann cell marker S100B and several keratins confirmed successful dissection of cNF tissue from the overlying skin. Hierarchical clustering showed extensive overlap between the tumor and skin samples in three out of four individuals, suggesting high overall similarity between the two tissue types. Based on the analysis of the GO terms, cNFs were associated with decreased expression of proteins related to cell proliferation, extracellular matrix remodeling, angiogenesis and cellular metabolism.</p><p><strong>Conclusion: </strong>The cNFs are relatively quiescent, consistent with their benign nature and limited growth potential. The development of pharmacological therapy for cNFs requires overcoming the high similarity between cNFs and the overlying skin. The present dataset can serve as a resource for future research on cNFs.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TIGIT antibody with PVR competitive ability enhances cancer immunotherapy and capable of eliciting anti-tumour immune memory.","authors":"Huijuan Yu, Shaowen Jin, Min Zeng, Zhiqing Yang, Xiaofei Wang","doi":"10.1038/s41416-025-03046-w","DOIUrl":"https://doi.org/10.1038/s41416-025-03046-w","url":null,"abstract":"<p><strong>Background: </strong>T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) is a checkpoint receptor thought to be involved in mediating T-cell exhaustion and dysfunction of natural killer (NK) cells in tumours and is emerging as novel promising targets in immunotherapy, however, the ligand binding and the efficacy of its antibody still need to be further explored.</p><p><strong>Methods: </strong>Four different TIGIT antibodies in characteristics of antigen binding, in vitro effects on activated T cells, Fc region functions and tumour inhibition in animal models were compared. The antibody as monotherapy and combined with anti-PD-L1 antibody, effects on PBMC in ex vivo coculture with autologous human CRC organoids as well as PK profile were evaluated.</p><p><strong>Results: </strong>Studies demonstrated that TIGIT antibody with PVR-competitive ability as monotherapy resulted in inhibition of tumour growth, sustained anti-tumour immune memory in tumour re-challenge mice, enhanced anti-tumour therapy in combination with anti-PD-L1. Ex vivo coculture assay suggested that TIGIT antibody treatment activated immune cells and promoted infiltration and tumour killing ability of autologous PBMC in human CRC organoids.</p><p><strong>Conclusions: </strong>Our study broadens the knowledge of TIGIT antibody in cancer immunotherapy and may benefit future development of next-generation checkpoint inhibitors with improved clinical outcomes.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}