International Journal of Cancer最新文献

Immune-checkpoint-inhibition (ICI) represents the mainstay for treatment of advanced gastroesophageal cancer (GEC) in most cases. Sex differences in innate and adaptive immune responses are known to reflect distinct anti-tumor efficacy of ICI in female and male patients. However, most randomized controlled trials (RCTs) on ICI in GEC were conducted without taking sex differences into account. To address this uncertainty, we conducted a meta-analysis across first-line (1L) RCTs in advanced GEC. Systematic research was performed up to March 31, 2025. The primary endpoint was the pooled hazard ratio (HR) for overall survival (OS) in male and female patients, comparing ICI-based therapy versus control. The secondary objective was to assess the interaction between sex and treatment effect. A total of 15 RCTs were included (7 trials on ESCC and 8 trials on GEA). In male ESCC patients, the pooled HR for OS favored ICI with statistical significance (HR = 0.70, 95% CI = 0.65-0.76, P < .00001). In women, HR was 0.81 (95% CI = 0.61-1.07, P = .14). In GEA, ICI- based therapy showed significant survival benefits in both men (HR = 0.78, 95% CI = 0.73-0.83, P < .00001) and women (HR = 0.82, 95% CI = 0.75-0.90, P < .0001). The test for interaction between sexes and treatment effect indicated no significant difference in ICI efficacy between sexes in ESCC (Chi² = 1.02, P = .31) and GEA (Chi² = 0.78, P = .38). In advanced ESCC, only men showed a statistically significant OS benefit from ICI-based treatment, but the difference between sexes was not statistically significant. In GEA, both sexes had similar survival benefits.

Clinical trials have shown that low-dose computed tomography (LDCT) screening reduces lung cancer mortality among selected groups of ever-smokers. Nordic countries have yet to implement lung cancer screening programs in part due to limited evidence on the associated health and economic consequences. This study evaluated the cost-effectiveness of LDCT screening compared with no screening for Norwegian individuals aged 50-74 years who ever smoked, using the Dutch-Belgian NELSON screening-eligibility criteria and trial outcomes. In addition, we evaluated the potential need and value of additional research to improve decision-making about LDCT screening implementation. We developed a probabilistic simulation model reflecting the Dutch-Belgian NELSON trial outcomes and Norwegian epidemiological, cost, and health-related quality-of-life data to evaluate long-term (discounted) health and economic consequences from an extended healthcare perspective. Model outputs included sex-stratified clinical and economic outcomes. Cost-effectiveness was summarized using incremental cost-effectiveness ratios (ICERs). Compared with no screening, NELSON-like LDCT screening provided an additional 0.043 quality-adjusted life-years (QALYs) per screened man for an additional $1286, yielding an ICER of $30,672 per QALY gained. For women, screening yielded greater health benefits and therefore a lower ICER (i.e., $22,249 per QALY gained), though there was greater uncertainty around health benefits. Additional analyses indicated potential value in collecting further evidence on screening-related outcomes to reduce decision uncertainty, particularly for women. Given Norwegian benchmarks for good value and achieving similar mortality benefits to the NELSON trial, LDCT lung cancer screening for individuals who ever smoked under "NELSON-like" criteria may be considered cost-effective for both men and women in Norway.

C-X-C motif chemokine ligand 5 (CXCL5), also known as epithelial neutrophil-activating peptide 78 (ENA-78), is a pivotal member of the ELR⁺ CXC chemokine family, characterized by a conserved glutamic acid-leucine-arginine motif. CXCL5 plays a central regulatory role in shaping the tumor immune microenvironment (TIME). Its expression is regulated by transcription factors (NF-κB, STAT3, SP1, p53), epigenetic modifications (DNA methylation, histone acetylation, microRNAs), and cytokines/growth factors (IL-1β, TNF, EGF). These regulatory mechanisms shape CXCL5 function in inflammation and cancer. CXCL5 interacts with diverse immune cells, including tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), T lymphocytes, and myeloid-derived suppressor cells (MDSCs). These interactions establish an immunosuppressive microenvironment that drives tumor immune evasion, metastasis, and therapeutic resistance. Mechanistically, CXCL5 regulates the malignant phenotypes of tumor cells by activating signaling pathways including PI3K/AKT, JAK-STAT/NF-κB, and ERK/MSK1/Elk-1/snail. Recent preclinical studies highlight that blocking the CXCL5-CXCR2 axis reverses immunosuppression and improves immune checkpoint inhibitor efficacy. This review systematically maps the multidimensional regulatory network of CXCL5 in the TIME and summarizes its molecular interactions with immune cells. The therapeutic potential of targeting these pathways is also explored to inform novel immunotherapeutic combination strategies.

Penile cancer is rare. It has been suggested that approximately half are human papillomavirus (HPV) associated, but large-scale studies on HPV prevalence and time trends are limited. We aimed to examine the high-risk HPV (hrHPV) prevalence in a large single-country study of penile squamous cell carcinomas (SCC) during a 26-year period. From the nationwide Danish Pathology Register, we identified all penile SCCs diagnosed during the period 1995-2020 at hospitals covering most regions in Denmark. Histologic slides were evaluated by expert pathologists, and archived tumor tissue was tested for the presence of HPV DNA using the INNO-LiPA assay. We assessed the overall and type-specific HPV prevalence according to calendar period, age, and histology, and estimated the annual percentage change (EAPC) of hrHPV positivity over the entire study period. We included 1040 penile SCCs. The overall HPV prevalence was 54.5% and the hrHPV prevalence was 50.4%. We observed no change in the prevalence of hrHPV over time (EAPC = -0.03% [95% confidence interval: -0.91; 0.85]). HPV16 was the most prevalent genotype (41.1%), and 50.0% of the penile SCCs had an HPV type that would be covered by the nine-valent HPV vaccine (HPV6/11/16/18/31/33/45/52/58). Penile SCCs with HPV-associated histological features had the highest hrHPV prevalence, particularly tumors exhibiting basaloid features (81.8%-87.7%). In this large population-based study, covering most regions in Denmark, we found no substantial change in hrHPV prevalence during 1995-2020. Our findings suggest that prophylactic vaccination with the nine-valent HPV vaccine could prevent a considerable part of penile SCCs in Denmark.

Langerhans cell histiocytosis (LCH) is a rare, heterogeneous inflammatory myeloid neoplasm. This study focuses to summarize real-world experiences of using mitogen-activated protein kinase (MAPK) inhibitors in managing pediatric LCH. Thirty-six children with LCH received vemurafenib (n = 11), dabrafenib (n = 19), or trametinib (n = 6), either as monotherapy (n = 24) or combined with chemotherapy (n = 12). The median Disease Activity Score declined from 5 at baseline to 1 after 3 months of MAPK inhibitor therapy (p < .0001). Elevated interleukin-2 receptor (IL-2R) and tumor necrosis factor-α (TNF-α) levels were observed in 90.1% and 81.8% of patients, respectively. Median IL-2R and TNF-α levels decreased from 1212 U/mL and 15 ρg/mL at baseline to 494 U/mL and 4.18 ρg/mL at 3 months (p < .0001, p = .002), with no significant differences between MAPK inhibitor alone and combined with chemotherapy groups (p = .7791, p = .7503). The objective response rate at 3 months was 94.4% (34/36). At last follow-up, 20 patients had no active disease (NAD); 13 had NAD with residual diabetes insipidus and/or sclerosing cholangitis; 1 had NAD with neurodegeneration; and 2 died of progressive disease. Among 13 patients who discontinued treatment, relapse occurred more frequently in the monotherapy group (75%) than in the combination group (20%), but the difference was not statistically significant (p = .103). [Correction added on 07 February 2026, after first online publication: The p value has been revised from .047 to .103.]. Grade ≥3 adverse events occurred in 11.1% and resolved with dose adjustment. MAPK inhibitors are effective and well tolerated in pediatric LCH. Combination therapy may reduce relapse risk. Further prospective studies are warranted.

The purpose of cancer screening is to reduce mortality, and ideally incidence, from the cancer screened for. Until recently, cancer screening has been offered to all persons in pre-defined sex- and age-groups. The exception is lung screening which is targeted to high-risk individuals. Evidence for effect of screening on cancer-specific mortality is available for cancer of the cervix, breast, colorectal, lung, and prostate, and on cancer-specific incidence for cervix and colorectal cancer. With more effective molecular and computational tools, the current paradigm of cancer screening will change. Manual reading of images and pathology in mammography, cytology, colposcopy, colonoscopy, and CT scan will be complemented or replaced by AI-interpretation. Risk stratification will diversify screening intensity, for instance in breast screening where modelling and randomized controlled trials are underway. Blood-based screening tests might allow for simultaneous early detection of several types of cancer. Furthermore, prediction models based on life trajectories in health and other data will enhance risk stratification, potentially dividing the population into groups with no need of screening, with need of simple or advanced screening, with need of surveillance or even diagnostics. In public health care systems, these developments must be closely monitored. Before replacing an existing program, evidence for non-inferiority in reducing cancer-specific mortality should be ensured. Benefits must outweigh harms, and citizens should have confidence in new screening schemes. With the pressure on health care resources, screening should continue in organized and monitored programs. Taking these conditions into account, the new screening tools will potentially enable improved cancer control.

Patients with lung squamous cell carcinoma (LUSC) are often diagnosed at advanced stages, limiting opportunities for early intervention. LUSC develops through multistep progression from low-grade lesions to high-grade lesions, including carcinoma in situ (CIS), of which about half progress to invasive cancer while the other half regress. Although frequent mutations and copy number alterations have been documented in LUSC and observed in precursor lesions, their prognostic significance in precancers remains largely unexplored. In this study, we leveraged gene expression data from LUSC tumors in The Cancer Genome Atlas to derive transcriptional signatures corresponding to 34 key driver genomic aberrations, including mutations, amplifications, and deletions. These tumor-derived signatures were applied to precancerous datasets to assess their ability to characterize developmental stages and predict progression risk. We found many of these signatures increased progressively across lesion stages, reflecting roles in early tumorigenesis. In particular, several signatures accurately predicted which CIS lesions would progress to invasive cancer. Furthermore, these signature scores were more strongly associated with prognosis in LUSC than the presence of genomic aberrations alone. We also examined relationships between driver-associated signatures and the tumor immune microenvironment. Signature scores were significantly correlated with immune features such as immune cell infiltration and immune checkpoint gene expression, including CD274 (PD-L1). These associations varied across stages, indicating dynamic immune interactions during cancer evolution. Together, our findings demonstrate that tumor-derived driver gene expression signatures provide valuable insight into the biology and progression risk of precancerous lesions, offering potential utility for early detection and intervention in LUSC.