International Journal of Cancer最新文献

{"title":"Sex specific familial risk in lung cancer through changing histologies in Sweden.","authors":"Kari Hemminki, Frantisek Zitricky, Kristina Sundquist, Jan Sundquist, Asta Försti, Akseli Hemminki","doi":"10.1002/ijc.35431","DOIUrl":"https://doi.org/10.1002/ijc.35431","url":null,"abstract":"<p><p>Familial clustering of lung cancer (LC) is related to shared smoking habits but the contribution of other potential factors such as sex or histology is not well known, and these are the subjects of the present study in Sweden. Family relationships (from Multigeneration register) and diagnosed cancers (from Cancer registry) were obtained from the national registers from 1961 to 2021. The overall familial risk for LC was constant from the 1990s but the male familial risk decreased while the female familial risk doubled at the same time when female incidence doubled. The female familial risk for mother-daughter pairs was higher (SIR = 2.2 [2.0-2.3], N = 716) than for father-son pairs (SIR = 1.6 [1.5-1.8], N = 962). The histology-specific familial risks for adenocarcinoma, squamous cell carcinoma, small cell and large cell carcinoma were highest for concordant histology but also present for discordant histology. The number of family members diagnosed with LC was a strong determinant of familial risk. The novel results showed that familial risk of LC depends on the background incidence of LC and is higher for women compared to men. We demonstrated further an increased familial risk for each of the four histological types of LC which was higher for concordant than discordant histologies but was even detected between discordant histologies suggesting that LC histology is not a genetic trait.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741728","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}

{"title":"The Nirmiti application: An innovative tool for extending CanReg5 analyses to cancer mortality and paediatric cancer.","authors":"Pratik Sawant, Sushama Saoba, Prithviraj Kadam, Deepak Gupta, Adarsh Kumar Ponnada, Divya Khanna, Suraj Perera, Ugyen Tshomo, Morten Ervik, Leslie Mery, Freddie Bray, Atul Budukh","doi":"10.1002/ijc.35420","DOIUrl":"https://doi.org/10.1002/ijc.35420","url":null,"abstract":"<p><p>The International Agency for Research on Cancer (IARC) Regional Hub in Mumbai provides technical support to population-based cancer registries (PBCRs) in South and South-East Asian (SSEA) countries. For data management and incidence rate table generation, the Hub recommends CanReg5, an open-source registry software developed by IARC, to all PBCRs seeking support from it. However, CanReg5 is limited in generating mortality and paediatric cancer incidence tables. Several SSEA cancer registries requested the Hub to develop practical solutions to facilitate the generation of cancer rates statistics. The IARC Regional Hub, in Mumbai, subsequently developed Nirmiti, an innovative web application which is capable of generating incidence, mortality, and paediatric cancer rates based on provided input data. The application accepts registry data in a specific format and generates required tables according to the selected options; users can input data from CanReg5 or other software into Nirmiti for processing. Nirmiti generates childhood cancer rates for age-groups 0-14 and 0-19, based on the 12 main groups and 47 subgroups of the International Incidence of Childhood Cancer, Volume 3, and is freely available to cancer registries upon request. The application has been successfully utilized by PBCRs in India, Sri Lanka, and Bhutan.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741729","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}

{"title":"Comparing outcomes and toxicities among patients with nasopharyngeal carcinoma treated with daytime versus evening radiotherapy: A retrospective analysis with propensity score matching.","authors":"Kaiqi Lan, Sailan Liu, Suchen Li, Xuesong Sun, Siyi Xie, Guodong Jia, Rui Sun, Haiqiang Mai","doi":"10.1002/ijc.35408","DOIUrl":"https://doi.org/10.1002/ijc.35408","url":null,"abstract":"<p><p>To compare survival outcomes and acute toxicities between daytime and evening radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). We enrolled 1351 NPC patients who received definitive RT in the daytime (before 16:00; n = 625) or evening (after 16:00; n = 726) between 2015 and 2016. Optimal cutoff time was determined by receiver operating characteristic analysis. Survival outcomes and toxicities were compared between groups before and after propensity score matching (PSM). Multivariate Cox analyses were performed to identify independent prognostic factors. With a median follow-up of 63 months, evening RT showed better overall survival (OS; p = 0.020), progression-free survival (PFS; p = 0.035), and locoregional failure-free survival (LRFS; p = 0.037), compared with daytime RT, but not distant metastasis-free survival (p = 0.523). Evening RT showed a lower incidence of all-grade dermatitis (59.5% vs. 68.2%, p = 0.002). After PSM, RT time remained an independent prognostic factor for LRFS (HR = 0.601, p = 0.018), OS (HR = 0.643, p = 0.043), and PFS (HR = 0.754, p = 0.040). Subgroup analyses revealed that evening RT improved OS (p = 0.007) and PFS (p = 0.006) in females and LRFS (p = 0.035) in males, with more pronounced benefits in older females (≥45 years; OS: p = 0.027, PFS: p = 0.003) and reduced mucositis in older males (82.9% vs. 91.4%, p = 0.015). Overall, evening RT demonstrated superior survival outcomes and reduced acute toxicities in NPC patients, with distinct benefits across sex and age.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741804","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}

{"title":"Screening outcomes at second FIT screening in individuals with a first time negative FIT-result or low-risk adenomas: Results from a nationwide FIT screening program.","authors":"Pernille Thordal Larsen, Susanne Fogh Jørgensen, Morten Rasmussen, Berit Andersen, Sisse Helle Njor","doi":"10.1002/ijc.35419","DOIUrl":"https://doi.org/10.1002/ijc.35419","url":null,"abstract":"<p><p>In Denmark, participants in faecal immunochemical test (FIT) screening with low-risk adenomas are recommended a return to biennial FIT-screening. However, they participate less than the FIT-negative group (FIT₁-negative) at subsequent screening. Further, it is not clear how much this group benefits from the subsequent screening. We aimed at comparing the CRC incidence before and at the next screening (FIT₂) in the low-risk group to that of those having a FIT-negative result at first time FIT-screening. In this register-based cohort study, we estimated the incidence of interval CRC (ICRC) and results of FIT₂, including the FIT₂-positivity rate and rate of screen detected CRC (SDCRC). Relative risk (RR) comparing the low-risk group to FIT₁-negatives was estimated. Adjustment for age and sex was performed with binary regression and presented with a 95% confidence interval (CI). Incidence of ICRC was 0.17% and 0.08% in the Low-risk group and FIT₁-negative group, respectively, RR 2.18 (95%CI 1.51; 3.16). After adjustment, RR was 1.76 (95%CI: 1.22; 2.55). The FIT₂-positivity rate was 14.4% and 4.4% for the Low-risk group and FIT₁-negative group, respectively. At FIT₂-screening, the detection of SDCRC was 0.36% and 0.16% in the low-risk and FIT₁-negative group, respectively, RR 2.27 (95%CI: 1.46; 3.54), adjusted 1.83 (95% CI: 1.17; 2.85). Despite a recent colonoscopy, participants having low-risk adenomas detected at first colonoscopy in FIT-screening remain at a higher short-term risk of ICRC and SDCRC compared to the FIT₁-negatives. Continuous participation in FIT-screening is important for the Low-risk group.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735575","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}

{"title":"Efficacy and safety of autologous CIK cell therapy plus Toripalimab with or without chemotherapy in advanced NSCLC: A phase II study.","authors":"Runbo Zhong, Tianqing Chu, Liwen Xiong, Chunlei Shi, Wei Zhang, Xueyan Zhang, Xiaohua Yang, Yuqing Lian, Mengqi Zhang, Hua Zhong, Baohui Han","doi":"10.1002/ijc.35422","DOIUrl":"https://doi.org/10.1002/ijc.35422","url":null,"abstract":"<p><p>Advanced non-small cell lung cancer (NSCLC) with positive PD-L1 expression requires more effective therapeutic options. This study aims to evaluate the efficacy and safety of autologous cytokine-induced killer (CIK) cell therapy combined with the anti-PD-1 antibody toripalimab, with or without chemotherapy, as a first-line treatment for advanced NSCLC. This phase II trial enrolled 40 patients with PD-L1-positive, driver mutation-negative advanced NSCLC between July 2020 and December 2022. Patients were randomly assigned to Arm A (toripalimab + CIK cells + chemotherapy) or Arm B (toripalimab + CIK cells). Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety profiles were evaluated. Subgroup analyses were conducted based on the number of CIK cell cycles received. Arm A showed a significantly longer median PFS compared to Arm B (20.0 vs. 6.0 months, p = 0.0038), while median OS was not reached in Arm A versus 17.0 months in Arm B (p = 0.0479). ORR was 47.4% in Arm A and 60.0% in Arm B. Patients receiving four or more cycles of CIK cells had significantly improved PFS and OS. No new safety concerns were identified. The combination of CIK cells and toripalimab, with or without chemotherapy, demonstrates promising efficacy and safety in patients with advanced PD-L1-positive NSCLC. The addition of chemotherapy may further enhance therapeutic outcomes, making it a potentially superior strategy compared to CIK cells combined with the anti-PD-1 antibody alone.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707929","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}

{"title":"Characterization of extrachromosomal circular DNA associated with genomic repeat sequences in breast cancer.","authors":"Wenxiang Lu, Lingsong Yao, Ying Wang, Fuyu Li, Bingbo Zhou, Wenlong Ming, Yali Jiang, Xiaoan Liu, Yun Liu, Xiao Sun, Yan Wang, Yunfei Bai","doi":"10.1002/ijc.35423","DOIUrl":"https://doi.org/10.1002/ijc.35423","url":null,"abstract":"<p><p>Extrachromosomal circular DNA (eccDNA) has emerged as a potential biomarker for disease due to its stable closed circular structure. However, the diagnostic utility of eccDNA remains underexplored. In this study, we demonstrate that the characteristics of eccDNA associated with genomic repetitive elements change in breast cancer patient tissues and plasma. These changes can serve as signatures for accurate cancer classification. We profiled eccDNA annotated to repeat elements across the genome in tissues and plasma, aggregating each repeat element to the superfamily and subfamily level. Our findings indicate that eccDNA associated with repetitive elements in cancer exhibits regular patterns of enrichment or depletion in specific elements, particularly at the family level. Additionally, these repeat element changes are present in different subtypes of breast cancer, correlated with varying hormone receptor expression. Although there are differences in the landscapes of eccDNA on repetitive elements between cancer tissues and paired plasma, the unique characteristics of eccDNA associated with repetitive sequences in the plasma of cancer patients facilitate better differentiation from normal individuals. These analyses reveal that changes in eccDNA associated with repeat sequences in human cancers can be used as diagnostic biomarkers for cancer patients.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707928","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}

{"title":"Prognosis prediction in non-Hodgkin lymphoma by assessing lymphoid organs uptake patterns using baseline ¹⁸F-FDG PET/CT.","authors":"Jie Ding, Xinwei Cheng, Haiyan Wang, Yu Sun, Yihong Yang, Na Qi, Yan Jiang, Xing Chen, Qingyuan Meng, Zhiwen You, Jianjuan Jiang, Jun Zhao","doi":"10.1002/ijc.35412","DOIUrl":"https://doi.org/10.1002/ijc.35412","url":null,"abstract":"<p><p>The prognostic implications of lymphoid organs (LOs) involvement in untreated non-Hodgkin lymphoma (NHL) patients remain underexplored. This study aims to explore the significance of LOs metabolic activity, assessed via ¹⁸F-FDG PET/CT, in predicting the early treatment response and prognosis of NHL patients. A retrospective analysis was conducted on ¹⁸F-FDG PET/CT imaging data of untreated NHL patients from March 2016 to December 2023. Metabolic activity levels of LOs were evaluated and scored. Prognostic parameters included the international prognostic index (IPI), progression-free survival (PFS), overall survival (OS), and the interim efficacy evaluation. The median follow-up time was 15 months. The survival analysis was conducted using Kaplan-Meier and Cox regression methods. We included a total of 125 NHL patients (63 ± 12 years) with baseline ¹⁸F-FDG PET/CT scans. Based on the metabolic scores of LOs, patients were divided into three groups: 36 (28.8%) in the low metabolism group, 64 (51.2%) in the intermediate metabolism group, and 25 (20.0%) in the high metabolism group. LOs metabolic scores emerged as an independent prognostic factor. Patients with high metabolic activity in LOs had significantly shorter PFS and OS compared to those with lower activity (OS HR = 4.56; PFS HR = 3.87; p <0.01). The combination of LOs metabolism and extra-LOs tumor burden can further stratify the risk in NHL patients. Metabolic activity in LOs in ¹⁸F-FDG is a vital prognostic indicator and may predict early treatment response in NHL patients. The incorporation of LOs metabolic assessment into clinical practice could enable more accurate prognosis and tailored treatment strategies.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699264","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}

{"title":"Low type-2 immune effectors modulate atopic diseases' protective role in pancreatic cancer risk.","authors":"Jiangchuan He, Bilal Alashkar Alhamwe, Sergio Sabroso, Alfredo Carrato, Manuel Hidalgo, Xavier Molero, Mar Iglesias, José Perea, Antoni Farré, Adonina Tardón, Enrique Dominguez-Muñoz, Victor Barberà, Luís Muñoz-Bellvís, Matthias Löhr, William Greenhalf, Michael O'Rorke, Thomas Gress, Tatjana Crnogorac-Jurcevic, Auba Gayà, Alberto Langtry, Jörg Kleeff, Rita Lawlor, Francisco X Real, Harald Renz, Núria Malats","doi":"10.1002/ijc.35397","DOIUrl":"https://doi.org/10.1002/ijc.35397","url":null,"abstract":"<p><p>Studies reported that atopic individuals exhibit a 36% reduced risk of developing pancreatic ductal adenocarcinoma (PDAC); however, the underlying molecular mechanisms remain unclear. This study examines the specific role of type-2 immune response in the atopy-PDAC inverse association. To endotype atopic conditions using type-2 immune effectors (i.e., eosinophils and immunoglobulin-E[IgE]) and investigate their protective effect against PDAC risk, IgE levels were measured in 688 PDAC cases and 558 controls from the PanGenEU case-control study. 'IgE-sensitization' was defined as having >100 kU/L total IgE with lab-tested sensitization to ≥1 food- or aeroallergens. Atopic conditions were determined using the European Community Respiratory Health Survey questionnaire. The UK Biobank cohort's 544 PDAC cases and 92,038 nested controls were categorized based on a threshold of 0.15 × 10⁹ eosinophil cells/L plus self-reported atopy. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Restricted cubic splines were applied to examine the nonlinear relationship between type-2 immune effectors and PDAC risk. PDAC risk was not linearly associated with type-2 immune effectors levels. Compared to low IgE-sensitized non-atopic individuals, the low IgE-sensitized atopic population had significantly reduced PDAC risk (OR = 0.56, 95% CI: 0.35-0.84). Similar trends were observed among atopic individuals with low eosinophil counts (OR = 0.67, 95% CI: 0.47-0.95). Atopic conditions were inversely associated with PDAC risk, particularly among those with low levels of type-2 immune effectors. This indicates the protective effect of atopy against PDAC risk is modulated by low type-2 immune response.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646576","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}

{"title":"Alcohol and smoking habits in association with hepatocellular carcinoma risk.","authors":"Elom K Aglago, Ines Ramos, Pekka Keski-Rahkonen, Chrysovalantou Chatziioannou, Heinz Freisling, Veronika Fedirko, Marc J Gunter, Christina C Dahm, Fie Langmann, Nicola Bondonno, Anne Tjønneland, Gianluca Severi, Therese Truong, Verena Katzke, Rudolf Kaaks, Manuela Bergmann, Matthias B Schulze, Giovanna Masala, Valeria Pala, Maria Santucci de Magistris, Chiara Di Girolamo, Marko Lukic, Inger Torhild Gram, Catalina Bonet, Maria-Jose Sánchez, María-Dolores Chirlaque, Pilar Amiano, Marcela Guevara, Roel Vermeulen, Jonas Manjer, Linda Eriksson, Tim J Key, Ana-Lucia Mayen, Laure Dossus, Elisabete Weiderpass, Alicia K Heath, Pietro Ferrari, Mazda Jenab","doi":"10.1002/ijc.35401","DOIUrl":"https://doi.org/10.1002/ijc.35401","url":null,"abstract":"<p><p>We assessed hepatocellular carcinoma (HCC) risk associated with smoking and alcohol consumption and their interactions, using both questionnaire data and objective serum biomarkers. Information on smoking and alcohol consumption was collected at baseline from 450,112 participants of the EPIC cohort, among whom 255 developed HCC after a median follow-up of 14 years. In a nested case-control subset of 108 HCC cases and 108 matched controls, known biomarkers of smoking (cotinine, nicotine) and habitual alcohol consumption (2-hydroxy-3-methylbutyric acid) were annotated from untargeted metabolomics features. Multivariable-adjusted hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were computed, and multiplicative and additive interaction parameters were calculated. Compared to never smokers, current smokers had a higher HCC risk (HR = 2.46, 95% CI = 1.77-3.43) dose-dependently with the number of cigarettes smoked per day (P_trend <.001). Compared to light drinkers, HCC risk was higher in former (HR = 3.20, 95% CI = 1.70-6.03), periodically heavy (HR = 1.98, 95% CI = 1.11-3.54), and always heavy (HR = 5.51, 95% CI = 2.39-12.7) drinkers. Higher HCC risk was also observed in the highest versus the lowest tertiles of cotinine (OR = 4.88, 95% CI = 1.52-15.70), nicotine (OR = 5.80, 95% CI = 1.33-25.30) and 2-hydroxy-3-methylbutyric acid (OR = 5.89, 95% CI = 1.33-26.12). Questionnaire-assessed smoking and alcohol exposures did not demonstrate an HCC risk interaction at the multiplicative (MI = 0.88, 95% CI = 0.40-1.96) or additive (RERI = 0.71, 95% CI = -10.1 to 23.6; attributable proportion = 0.17, 95% CI = -0.52 to 1.16; synergy index = 1.27, 95% CI = 0.98-1.66) scales. Similar analyses with cotinine, nicotine, and 2-hydroxy-3-methylbutyric acid also did not show interactions between smoking and alcohol consumption on HCC risk. Smoking and alcohol consumption are strong independent risk factors for HCC and do not appear to synergistically impact its risk, but larger studies are needed.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646571","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}

{"title":"TNF signature in advanced melanoma patients treated with immune checkpoint inhibitors: Results from the MELANFα clinical study.","authors":"Mathieu Virazels, Amélie Lusque, Stéphanie Brayer, Matthieu Genais, Carine Dufau, Jean Milhès, Thomas Filleron, Cécile Pagès, Vincent Sibaud, Laurent Mortier, Olivier Dereure, Maha Ayyoub, Amandine Fabre, Nathalie Andrieu-Abadie, Vera Pancaldi, Céline Colacios, Nicolas Meyer, Bruno Ségui, Anne Montfort","doi":"10.1002/ijc.35416","DOIUrl":"https://doi.org/10.1002/ijc.35416","url":null,"abstract":"<p><p>Resistance to immune checkpoint inhibitors (ICI) in cancer patients is not fully understood, and predictive biomarkers are lacking. MELANFα (NCT03348891) is an open-label, prospective, multicenter cohort of 60 patients with advanced melanoma receiving ICI (bitherapy: ipilimumab + nivolumab; monotherapy: pembrolizumab or nivolumab). The primary objective was to evaluate whether changes in plasma TNF between baseline (W0) and week 12 (W12) identified patients with non-progressive disease at W12. Secondary and exploratory objectives were to assess the association between plasma TNF, tumor response, and changes in circulating T cells. Plasma TNF increased along therapy, but its W12/W0 fold change was not associated with non-progressive disease at W12. However, plasma TNF levels at W12 were significantly higher in non-responders than in responders across therapies (p = .0129). The remodeling of circulating T cell subpopulations was mostly triggered by bitherapy. Increased proportions of circulating central memory and effector memory CD8 T cells after bitherapy were positively and negatively associated with response to treatment, respectively. In this cohort, circulating T cells from responders and non-responders also displayed distinct molecular characteristics. Indeed, responders showed an increased proportion of CD8 T cells with low enrichment of TNF-related pathways and high cytotoxic potential, while non-responders displayed increased proportions of circulating CD8 EM T cells enriched for TNF-related pathways and directed toward cytokine expression. In conclusion, our study shows that elevated plasma TNF and enriched TNF pathways in T cells are associated with poorer clinical outcomes, reinforcing the notion that TNF may dampen ICI efficacy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646581","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}