International Journal of Cancer最新文献

{"title":"CD8⁺ T cells in patients with hypopharyngeal squamous cell carcinoma are susceptible to radiation-induced damage.","authors":"Hanqing Lin, Jingyu Ma, Yu Heng, Xiaoke Zhu, Qiuyan Jin, Xuping Ding, Lei Tao, Liming Lu","doi":"10.1002/ijc.35329","DOIUrl":"https://doi.org/10.1002/ijc.35329","url":null,"abstract":"<p><p>Radiotherapy (RT) is a commonly used clinical management for hypopharyngeal squamous cell carcinoma (HPSCC), which represents the most unfavorable prognosis among all subtypes of head and neck squamous cell carcinoma. However, radiation may cause lymphopenia, a significantly adverse event with detrimental prognostic implications for patients. While CD8⁺ T cells are vital in tumor immunity, the specific effects of RT on CD8⁺ T cells as well as the underlying mechanisms have not been clearly elucidated. Here we found that subpopulations of peripheral T lymphocytes exhibited differential profiles in patients with HPSCC compared to healthy individuals both pre- and post-irradiation. Importantly, CD8⁺ T cells from HPSCC patients showed greater reduction of cytokine production, more severe proliferation defect, and increased apoptosis compared to those from healthy individuals after in vitro irradiation. Mechanistically, the ATM-Chk2 pathway mediated the enhanced apoptosis of CD8⁺ T lymphocytes from HPSCC patients upon irradiation. Therefore, our study demonstrated that CD8⁺ T cells in patients with HPSCC exhibit a higher susceptibility to radiation-induced damage compared to those in healthy individuals. The ATM-Chk2 pathway represents a potential immunotherapeutic target for safeguarding CD8⁺ T cells in HPSCC patients against radiation-induced apoptosis.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363381","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":"Predisposing conditions in patients with small intestinal adenocarcinomas in the Netherlands: A 20-year nationwide cohort study.","authors":"Jasmijn D G Linssen, Pascale J M Schafrat, Tim R de Back, Felice N van Erning, Monique E van Leerdam, Evelien Dekker, Louis Vermeulen, Ignace H J T de Hingh, Dirkje W Sommeijer","doi":"10.1002/ijc.35354","DOIUrl":"https://doi.org/10.1002/ijc.35354","url":null,"abstract":"<p><p>Small intestinal adenocarcinomas (SIAs) are associated with predisposing conditions, including inflammatory bowel disease (IBD) and celiac disease, but also genetic syndromes such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP). This nationwide cohort study investigated the incidence of genetic and non-genetic predisposing conditions in SIA and their influence on tumor characteristics and clinical features. Data were obtained from the Netherlands Cancer Registry. The incidence, characteristics, and clinical features per predisposing condition were analyzed in 2697 SIA patients diagnosed from 1999 through 2019. Of all SIA patients, 5.6% were known to have a genetic predisposing syndrome, of whom 4.0% had LS and 1.6% had a polyposis syndrome. In addition, 6.8% of SIA patients had a non-genetic predisposing condition: 3.9% IBD and 2.9% celiac disease. SIAs of patients with such predisposing syndromes or conditions were diagnosed at a younger age and earlier stage and affected the duodenum less often as compared to sporadic SIA patients. Both genetic and non-genetic predisposing conditions were associated with significantly better overall survival (OS) compared to sporadic SIA: sporadic SIA (median OS: 13.0 months, 95% CI: 11.8-14.2), LS (213.1 months, 99.3-NA), polyposis syndromes (61.3 months, 19.7-NA), IBD (29.5 months, 20.3-69.8), and celiac disease (50.4 months, 24.6-124.7). This nationwide cohort study shows significant differences between SIA with and without predisposing conditions and highlights the need for research on underlying molecular mechanisms to improve outcomes of SIA patients.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187870","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":"Immunoglobulin-like transcript 5 polarizes M2-like tumor-associated macrophages for immunosuppression in non-small cell lung cancer.","authors":"Huijun Xu, Xuebing Fu, Shuyun Wang, Yihui Ge, Lu Zhang, Juan Li, Fang Zhang, Yang Yang, Yifu He, Yuping Sun, Aiqin Gao","doi":"10.1002/ijc.35360","DOIUrl":"https://doi.org/10.1002/ijc.35360","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have shifted the treatment paradigm of non-small cell lung cancer (NSCLC) over the last decade. Despite notable therapeutic advancements in responders, the response rate remains limited owing to the immunosuppressive tumor microenvironment (TME). Therefore, to improve the efficacy of ICIs, it is essential to explore alternative targets or signals that mediate immunosuppression. Immunoglobulin-like transcript (ILT) 5 is a negative regulator of immune activation in myeloid cells. However, the expression and function of ILT5 in NSCLC remain unknown. Here, we found that ILT5 was highly expressed in tumor-associated macrophages (TAMs) of NSCLC tissues and predicted poor patient survival. Functionally, ILT5 induces the M2-like polarization of TAMs, which subsequently decreases the density of T cells, and increases FOXP3⁺T cell accumulation, leading to an immunosuppressive TME. The combination of ILT5 expression with M2-like TAM density is a more reliable biomarker of patient survival than ILT5 expression alone. ILT5 knockout mitigates the reprogramming of TAM and T cell subsets toward immunosuppressive phenotypes and inhibits tumor growth in vivo. These findings highlight that ILT5 is a potential immunotherapeutic target and a promising prognostic biomarker for NSCLC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254262","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":"Baseline audiometric assessment of newly diagnosed nasopharyngeal carcinoma patients: a multicentre cross-sectional study.","authors":"Housheng Wang, Ting Fan, Yushuang Lu, Lilin Que, Bin Zou, Lulu Huang, Fuli Chen, Xian Liang, Zhiling Shi, Qianxin Hu, Tingzhuang Yi, Leifeng Liang, Kai Hu","doi":"10.1002/ijc.35358","DOIUrl":"https://doi.org/10.1002/ijc.35358","url":null,"abstract":"<p><p>Hearing impairment is one of the most common chief complaints in newly diagnosed nasopharyngeal carcinoma (NPC) patients, but baseline audiometric assessments are seldom reported. This study aims to investigate the prevalence of hearing impairment in this population through comprehensive audiometric testing and analyse the associated factors. A cohort of 187 newly diagnosed NPC patients were recruited from three hospitals. Pre-treatment comprehensive audiometric assessments, including pure-tone audiometry, tympanometry, Eustachian tube function tests and distortion product otoacoustic emissions (DPOAE), were performed to evaluate hearing impairment. Patient characteristics and tumour invasion extent were also recorded. Binary logistic regression was employed to analyse factors associated with hearing impairment. Among the patients, 27.5% of ears showed conductive hearing loss (CHL), 13.6% had sensorineural hearing loss (SNHL), and 10.4% demonstrated mixed hearing loss. Additionally, 43.6% of ears exhibited abnormal tympanograms, 86.1% had Eustachian tube dysfunction, and 77.3% failed the DPOAE test. Multivariable analysis identified subjective hearing symptoms, mastoiditis, and invasion of the tensor veli palatini muscle and Eustachian tube as factors associated with CHL. T stage, mastoiditis, and invasion of the tensor veli palatini muscle and nasal cavity were linked to abnormal tympanograms. T stage, sinusitis, and invasion of the levator veli palatini muscle significantly affected Eustachian tube function, while age influenced both SNHL and DPOAE results. Hearing impairment is prevalent among newly diagnosed NPC patients, with over half exhibiting various forms. Comprehensive baseline audiometric assessment in this population is crucial for developing individualized treatment strategies and enabling early intervention to prevent further hearing deterioration.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187809","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":"p16/ki-67 dual stain triage of individuals positive for HPV to detect cervical precancerous lesions.","authors":"Diane M Harper, Tamera Paczos, Ruediger Ridder, Warner K Huh","doi":"10.1002/ijc.35353","DOIUrl":"https://doi.org/10.1002/ijc.35353","url":null,"abstract":"<p><p>p16/Ki-67 dual stain is a biomarker-based test that can identify oncogenic transformation in cervical cells with higher sensitivity than cervical cytology, using the same samples taken for human papillomavirus (HPV) testing and liquid-based cytology. Dual stain is approved by the US Food and Drug Administration (FDA) for triage of women with positive results by primary HPV testing or by HPV/cytology co-testing and has recently been incorporated into management guidelines. In this review, we summarize the data showing the utility of dual stain in detecting precancers, reducing the number of unnecessary colposcopies, and reassuring women who test negative. We also discuss the implications of dual stain for future treatment practice and health economics.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121868","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 gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.","authors":"Doratha A Byrd, Victoria Damerell, Maria F Gomez Morales, Stephanie R Hogue, Tengda Lin, Jennifer Ose, Caroline Himbert, Mmadili N Ilozumba, Christoph Kahlert, David Shibata, Adetunji T Toriola, Christopher I Li, Jane Figueiredo, W Zac Stephens, Christy A Warby, Sheetal Hardikar, Erin M Siegel, June Round, Cornelia M Ulrich, Biljana Gigic","doi":"10.1002/ijc.35342","DOIUrl":"10.1002/ijc.35342","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HR_rectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062472","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":"Enhancer-dependent gene regulation in space, time, and malignancies.","authors":"Belinda Blum, Victoria Dachtler, Angelika Feldmann","doi":"10.1002/ijc.35350","DOIUrl":"https://doi.org/10.1002/ijc.35350","url":null,"abstract":"<p><p>Control of cell-type-specific gene activation requires the coordinated activity of distal regulatory elements, including enhancers, whose inputs must be temporally integrated. Dysregulation of this regulatory capacity, such as aberrant usage of enhancers, can result in malignant transformation of cells. In this review, we provide an overview of our current understanding of enhancer-driven gene regulation and discuss how this activity may be integrated across time, followed by epigenetic and structural alterations of enhancers in cancers.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062260","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":"Evaluation of plasma alpha-1-antichymotrypsin as a marker for pulmonary Kaposi sarcoma.","authors":"Angela Nalwoga, Conner Jackson, Suzanne Fiorillo, Felix Manyeruke, Tobias Makoni, Tatenda Nyagura, Irene E White, Eric Rapaport, Rosemary Rochford, Margaret Borok, Thomas B Campbell","doi":"10.1002/ijc.35351","DOIUrl":"https://doi.org/10.1002/ijc.35351","url":null,"abstract":"<p><p>Individuals with AIDS and Kaposi sarcoma (AIDS-KS) with pulmonary involvement have high-risk of poor outcomes but diagnosis of pulmonary KS in low-resource settings is difficult. We aimed to discover plasma proteins that distinguish individuals with pulmonary KS from those without pulmonary involvement. SomaScan proteomics screen measured 7288 plasma proteins in 22 cases and 17 controls selected from 181 participants with HIV-1 and cutaneous KS who underwent bronchoscopy. Cases had KS in the lower respiratory tract by bronchoscopy. Controls had no KS lesions detected by bronchoscopy. Results of the proteomics screen were confirmed by ELISA measurement of plasma alpha-1-antichymotrypsin (SERPINA3) in 18 cases and 13 controls and in an additional 162 individuals with AIDS-KS who were not included in the case-control analysis. Proteomics identified 12 plasma proteins with differential levels in controls and cases. Plasma alpha-1-antichymotrypsin (SERPINA3) complex was consistently higher in cases compared to controls in the proteomics assay. Measurement of plasma alpha-1-antichymotrypsin by ELISA confirmed higher levels in cases (median 399.4, IQR 95.77-766.4 μg/ml) versus controls (median 39.98, IQR 31.2-170.2 μg/ml; p = .001). Plasma alpha-1-antichymotrypsin correlated with the estimated burden of pulmonary KS in the respiratory tract (r = 0.439; p = .0002) and 234 μg/ml had 51% sensitivity and 94% specificity for detection of pulmonary KS by bronchoscopy. Measurement of plasma alpha-1-antichymotrypsin has potential for identifying persons with pulmonary AIDS-KS and estimating the burden of KS in the lower respiratory tract.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062291","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":"How many people in the US are eligible for and respond to checkpoint inhibitors: An empirical analysis.","authors":"Alyson Haslam, Timothée Olivier, Vinay Prasad","doi":"10.1002/ijc.35347","DOIUrl":"https://doi.org/10.1002/ijc.35347","url":null,"abstract":"<p><p>In 2018, we estimated that eligibility for and response to immune checkpoint inhibitor (ICI) therapies were 44% and 12%, respectively. Since these estimates were published, there have been additional approvals. We sought to provide updated estimates of the percentage of patients with advanced and/or metastatic cancers in the US who are eligible for and respond to immune checkpoint inhibitors (ICIs). Using a cross-sectional analysis (2011-2023) of US Food and Drug Administration approvals (FDA) and deaths reported by the American Cancer Society, we estimated the percentage of patients in the US with advanced or metastatic cancers who are eligible and respond to ICI therapies and the long-term response of ICI drugs. Eleven ICI drugs have been approved for 20 tumor types in the metastatic setting. The estimated eligibility for ICIs increased from 1.54% in 2011 to 56.55% in 2023. The estimated response to ICIs increased from 0.14% in 2011 to 20.13% in 2023. The tumor types with the highest contribution to response and eligibility estimates in 2023 were non-small-cell lung cancer with PD-L1 expression ≤50% and PD-L1 expression >50%. Sixteen drug approvals had long-term progression-free survival (PFS) data available at 3 years follow-up, and 2 had PFS data at 5 years follow-up. Estimated eligibility and response have increased over time, but many people with advanced or metastatic cancers are currently ineligible for ICIs. Only about one-fifth of the patients will respond. Given the wide range of uses, the cost implications of ICIs globally are large.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062376","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":"United by Unique: A call for people-centred cancer care on World Cancer Day 2025.","authors":"Cary Adams","doi":"10.1002/ijc.35357","DOIUrl":"https://doi.org/10.1002/ijc.35357","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062479","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}