Gut最新文献

{"title":"Low-coverage whole genome sequencing of low-grade dysplasia strongly predicts advanced neoplasia risk in ulcerative colitis.","authors":"Ibrahim Al Bakir, Kit Curtius, George D Cresswell, Heather E Grant, Nadia Nasreddin, Kane Smith, Salpie Nowinski, Qingli Guo, Hayley L Belnoue-Davis, Jennifer Fisher, Theo Clarke, Christopher Kimberley, Maximilian Mossner, Philip D Dunne, Maurice B Loughrey, Ally Speight, James E East, Nicholas A Wright, Manuel Rodriguez-Justo, Marnix Jansen, Morgan Moorghen, Ann-Marie Baker, Simon J Leedham, Ailsa L Hart, Trevor A Graham","doi":"10.1136/gutjnl-2024-333353","DOIUrl":"10.1136/gutjnl-2024-333353","url":null,"abstract":"<p><strong>Background: </strong>The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This is a major challenge for effective clinical management.</p><p><strong>Objective: </strong>We aimed to provide accurate AN risk stratification in UC patients with LGD. We hypothesised that the pattern and burden of somatic genomic copy number alterations (CNAs) in LGD lesions could predict future AN risk.</p><p><strong>Design: </strong>We performed a retrospective multicentre validated case-control study using n=270 LGD samples from n=122 patients with UC. Patients were designated progressors (n=40) if they had a diagnosis of AN in the ~5 years following LGD diagnosis or non-progressors (n=82) if they remained AN-free during follow-up. DNA was extracted from the baseline LGD lesion, low-coverage whole genome sequencing performed and data processed to detect CNAs. Survival analysis was used to evaluate CNAs as predictors of future AN risk.</p><p><strong>Results: </strong>CNA burden was significantly higher in progressors than non-progressors (p=2×10^-6 in discovery cohort) and was a very significant predictor of AN risk in univariate analysis (OR=36; p=9×10^-7), outperforming existing clinical risk factors such as lesion size, shape and focality. Optimal risk prediction was achieved with a multivariate model combining CNA burden with the known clinical risk factor of incomplete LGD resection. Within-LGD lesion genetic heterogeneity did not confound risk prediction.</p><p><strong>Conclusion: </strong>Measurement of CNAs in LGD is an accurate predictor of AN risk in inflammatory bowel disease and is likely to support clinical management.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064949","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":"Revisiting the role of sphincterotomy in sphincter of Oddi disorder: a critical appraisal of the RESPOnD study.","authors":"Xuefan Zeng","doi":"10.1136/gutjnl-2025-334837","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334837","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"54 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062070","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":"EMERALD in the making? A promising blood-based microRNA panel to detect oesophageal adenocarcinoma and Barrett’s oesophagus","authors":"Prasad G Iyer","doi":"10.1136/gutjnl-2025-334795","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334795","url":null,"abstract":"Screening for oesophageal adenocarcinoma (OAC), a lethal cancer, when diagnosed after the onset of symptoms, and its sole known precursor, Barrett’s oesophagus (BO), though suggested by guidelines, remains underused.1 Support for screening is underpinned by level 1 evidence demonstrating the ability of endoscopic therapy of BO dysplasia to prevent progression to OAC and the excellent survival of patients with T1 OAC treated with endoscopic therapy.2 While multifactorial, a major obstacle to screening is thought to be the need for endoscopy (which is invasive and expensive with limited access) for BO detection. This has prompted efforts to develop non-endoscopic and non-physician-administered screening tools, which could lead to greater utilisation in practice. To this end, excellent performance characteristics and safety of swallowable cell collection devices+biomarkers in detecting BO (with and without OAC/dysplasia)3 have been reported, leading to the inclusion of this technology as an alternative to endoscopy, in guidelines. In a pragmatic clinical trial, 39% of approached patients expressed interest in this strategy.4 Another study reported that up to 60% of surveyed patients expressed interest in a capsule sponge+biomarker-based test, suggesting additional advantage with minimally invasive technologies.5 To this end, Miyoshi et al report promising results of a six-microRNA (miRNA) panel assayed in peripheral blood samples in detecting the presence …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"16 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054940","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":"Fasting-mimicking diet-enriched Bifidobacterium pseudolongum suppresses colorectal cancer by inducing memory CD8+ T cells","authors":"Ke Nan, Ziwen Zhong, Ying Yue, Yang Shen, Hao Zhang, Zhiqiang Wang, Kameina Zhuma, Baichao Yu, Ying Fu, Luman Wang, Xingfeng Sun, Mengdi Qu, Zhaoyuan Chen, Miaomiao Guo, Jie Zhang, Yiwei Chu, Ronghua Liu, Changhong Miao","doi":"10.1136/gutjnl-2024-333020","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333020","url":null,"abstract":"Background Fasting-mimicking diet (FMD) boosts the antitumour immune response in patients with colorectal cancer (CRC). The gut microbiota is a key host immunity regulator, affecting physiological homeostasis and disease pathogenesis. Objective We aimed to investigate how FMD protects against CRC via gut microbiota modulation. Design We assessed probiotic species enrichment in FMD-treated CRC mice using faecal metagenomic sequencing. The candidate species were verified in antibiotic-treated conventional and germ-free mouse models. Immune landscape alterations were evaluated using single-cell RNA sequencing and multicolour flow cytometry. The microbiota-derived antitumour metabolites were identified using metabolomic profiling. Results Faecal metagenomic profiling revealed Bifidobacterium pseudolongum enrichment in FMD-treated CRC mice. B. pseudolongum mediates the FMD antitumour effects by increasing the tissue-resident memory CD8+ T-cell (TRM) population in CRC mice. The level of L-arginine, a B. pseudolongum functional metabolite, increased in FMD-treated CRC mice; furthermore, L-arginine induced the TRM phenotype in vivo and in vitro. Mechanistically, L-arginine is transported by the solute carrier family 7-member 1 (SLC7A1) receptor in CD8+ T cells. Both FMD and B. pseudolongum improved anti-CTLA-4 efficacy in the orthotopic mouse CRC model. In FMD-treated patients with CRC, the CD8+ TRM cell number increased as B. pseudolongum and L-arginine accumulated. The abundance of CD8+ TRM cells and B. pseudolongum was associated with a better prognosis in patients with CRC. Conclusion B. pseudolongum contributes to the FMD antitumour effects in CRC by producing L-arginine. This promotes CD8+ T-cell differentiation into memory cells. B. pseudolongum administration is a potential CRC therapeutic strategy. All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article or uploaded as online supplemental information. The metagenomic sequencing data reported in this study are available at the National Centre for Biotechnology Information (NCBI) sequence-read archive database (Bio-Project ID: PRJNA1091840). All other data are available in the manuscript including its supplementary files from the lead contact, Changhong Miao (Miaochangh@hotmail.com) on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"206 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050053","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":"In vitro microbiota model recapitulates and predicts individualised sensitivity to dietary emulsifier","authors":"Héloïse Rytter, Sabrine Naimi, Gary Wu, Jim Lewis, Maeva Duquesnoy, Lucile Vigué, Olivier Tenaillon, Eugeni Belda, Marta Vazquez-Gomez, Nina Touly, Djésia Arnone, Fuhua Hao, Ruth E Ley, Karine Clément, Laurent Peyrin-Biroulet, Andrew D Patterson, Andrew T Gewirtz, Benoit Chassaing","doi":"10.1136/gutjnl-2024-333925","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333925","url":null,"abstract":"Background Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals. Objectives This study aimed to establish an approach for predicting an individual’s sensitivity to dietary emulsifiers via their baseline microbiota. Design We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor’s sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity. Results Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had microbiotas that were highly perturbed by CMC exposure in the MBRA model. CMC-induced microbiota perturbability was associated with a baseline metagenomic signature, suggesting the possibility of using one’s metagenome to predict sensitivity to dietary emulsifiers. Transplant of human microbiotas that the MBRA model deemed CMC-sensitive, but not those deemed insensitive, into IL-10−/− germfree mice resulted in overt colitis following CMC feeding. Conclusion These results suggest that an individual’s sensitivity to emulsifier is a consequence of, and can thus be predicted by, examining their baseline microbiota, paving the way to microbiota-based personalised nutrition. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"35 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044135","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":"Risk factors for pancreatic cancer in individuals with intraductal papillary mucinous neoplasms and no high-risk stigmata during up to 5 years of surveillance: a prospective longitudinal cohort study","authors":"Tsuyoshi Hamada, Hiroki Oyama, Daniel Nevo, Shuichi Tange, Shinya Takaoka, Yoshikuni Kawaguchi, Kazunaga Ishigaki, Kensaku Noguchi, Tomotaka Saito, Tatsuya Sato, Tatsunori Suzuki, Naminatsu Takahara, Mariko Tanaka, Kiyoshi Hasegawa, Tetsuo Ushiku, Yousuke Nakai, Maxim S Petrov, Mitsuhiro Fujishiro","doi":"10.1136/gutjnl-2024-333259","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333259","url":null,"abstract":"Background Cyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs). Objective To examine the above factors in relation to future risk of incident pancreatic carcinoma in individuals with IPMNs harbouring no high-risk stigmata. Design In a prospective longitudinal cohort, we analysed 2549 patients with IPMNs. A multivariable cause-specific Cox proportional hazards regression model was built to estimate HRs for incident pancreatic carcinoma. Results IPMN size at baseline and its annual growth rate over 2 years of follow-up were associated with incident pancreatic carcinoma (ptrend<0.001). The multivariable cause-specific HR per 10 mm increase in IPMN size was 1.28 (95% CI 1.10 to 1.50). The annual growth rates of 1.5–2.4 mm/year and ≥2.5 mm/year over 2 years were associated with multivariable cause-specific HRs of 1.91 (95% CI 0.78 to 4.67) and 4.52 (95% CI 2.28 to 8.98), respectively (vs <1.5 mm/year). Neither IPMN size at 5 years nor its maximum growth rate during 5 years was associated with incident pancreatic carcinoma (ptrend>0.07). MPD diameter at 5 years was associated with incident pancreatic carcinoma (multivariable cause-specific HR per 2 mm increase, 2.12; 95% CI 1.72 to 2.63). A predictive nomogram was generated for calculating the risk of incident pancreatic carcinoma. Conclusion IPMN size and its growth rate predict future pancreatic carcinoma risk only during first 5 years of follow-up. MPD diameter at 5 years may identify patients who still harbour a high risk for pancreatic carcinoma. Data are available on reasonable request. The deidentified data and analytical methods used in the current study will be available from the corresponding author on reasonable request.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"14 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049669","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":"Predictors of response to low-dose amitriptyline for irritable bowel syndrome and efficacy and tolerability according to subtype: post hoc analyses from the ATLANTIS trial","authors":"Alexandra Wright-Hughes, Pei-Loo Ow, Sarah L Alderson, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Catherine Fernandez, Elspeth A Guthrie, Delia P Muir, Christopher A Taylor, Amanda J Farrin, Hazel A Everitt, Alexander C Ford","doi":"10.1136/gutjnl-2024-334490","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334490","url":null,"abstract":"Background Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial. Objective To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA. Design ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype. Results There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs <50 on the IBS severity scoring system (IBS-SSS) (interaction p=0.048, mean difference in ≥50 years subgroup −46.5; 95% CI −74.2 to −18.8, p=0.0010), and subjective global assessment of relief (interaction p=0.068, OR in ≥50 years subgroup 2.59; 95% CI 1.47 to 4.55, p=0.0010), and those in the 70% most deprived areas of England compared with the 30% least deprived for a ≥30% improvement in abdominal pain (interaction p=0.021, OR in 70% most deprived subgroup 2.70; 95% CI 1.52 to 4.77, p=0.0007). Stronger treatment effects were seen in men, with higher Patient Health Questionnaire-12 scores, and with IBS with diarrhoea. Mean differences in individual IBS-SSS components favoured amitriptyline, and side effects were similar, across almost all IBS subtypes. Conclusion These exploratory analyses demonstrate there are unlikely to be deleterious effects of amitriptyline in any particular IBS subtype and could help identify patients in whom amitriptyline may be more effective. Trial registration number [ISRCTN48075063][1]. Data are available on reasonable request. All data requests should be submitted to the corresponding author, ACF, for consideration and would be subject to review by a subgroup of the trial team, which will include the data guarantor, AJF. Access to anonymised data may be granted following this review. All data-sharing activities would require a data-sharing agreement. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN48075063","PeriodicalId":12825,"journal":{"name":"Gut","volume":"63 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034975","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":"Metabolic dysfunction-associated steatotic liver disease in children","authors":"Nidhi P Goyal, Stavra Xanthakos, Jeffrey B Schwimmer","doi":"10.1136/gutjnl-2023-331090","DOIUrl":"https://doi.org/10.1136/gutjnl-2023-331090","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is the most common cause of chronic liver disease in children. MASLD encompasses a spectrum of liver disease and can be severe, with 10% of affected children presenting with advanced fibrosis. While biopsy remains the most accurate method for diagnosing and staging the disease, MRI proton density fat fraction and magnetic resonance elastography are the most reliable non-invasive measures for assessing steatosis and fibrosis, respectively. MASLD is associated with multiple comorbidities including type 2 diabetes, hypertension, dyslipidaemia, decreased bone mineral density, obstructive sleep apnoea, anxiety and depression. Currently, there are no pharmacological treatments available for children, highlighting the urgent need for paediatric clinical trials. A diet low in free sugars is promising for reducing steatosis and decreasing alanine aminotransferase, a surrogate marker for hepatic inflammation. Emerging data indicate that steatosis can be present in children under 6 years of age, which was previously considered rare. The intricate interplay of genetics may inform future therapeutics and prognostication, with the PNPLA3 gene showing the most evidence for association with the risk and severity of steatotic liver disease and steatohepatitis. MASLD is a complex disease affecting one in ten children and is associated with increased early mortality risk. More dedicated studies are needed in children to advance our understanding of this disease and find effective treatments.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"5 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027176","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 unusual cause of oesophageal stricture","authors":"Ya-Qi Gao, Jian-Chen Fang, Yun Cui, Jing-Yuan Fang, Dan-Feng Sun","doi":"10.1136/gutjnl-2025-334729","DOIUrl":"https://doi.org/10.1136/gutjnl-2025-334729","url":null,"abstract":"A 57-year-old woman presented to the Gastrointestinal Department with recurrent odynophagia and dysphagia for about 5 years. She also reported a 5-year history of oral soreness and multiple chronic oral ulcers, which were empirically diagnosed with lichen planus without biopsy in a local hospital and treated with steroids intermittently. She underwent upper gastrointestinal endoscopy three times during the last 5 years. Each endoscopy revealed mild stricture in the upper oesophagus with erosions or erythema. Histology results showed mainly inflammation. She was treated for Helicobacter pylori eradication and prescribed with proton pump inhibitors, but her symptoms remained. The physical examination was unremarkable except for mild oral erosions. Her skin was intact, without apparent lesions. Upper gastrointestinal endoscopy was performed again in our hospital, which revealed a whitish mucosa with mild stricture in the proximal third of the oesophagus (figure 1A–B). Stripping of …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"8 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020404","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":"Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation","authors":"Panagiota Maravelia, Haidong Yao, Curtis Cai, Daniela Nascimento Silva, Jennifer Fransson, Ola B Nilsson, Yong-Chen William Lu, Patrick Micke, Johan Botling, Francesca Gatto, Giulia Rovesti, Mattias Carlsten, Matti Sallberg, Per Stål, Carl Jorns, Marcus Buggert, Anna Pasetto","doi":"10.1136/gutjnl-2024-334148","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334148","url":null,"abstract":"Background Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy. Objective We evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment. Design T cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing. Results Bioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes. Conclusion These findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC. Data are available upon reasonable request. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental material.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"28 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991463","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}