CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.

ABSTRACT

The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.

PMID:42713910 | PMC:PMC13555834 | DOI:10.3322/caac.70100

CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.

ABSTRACT

The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.

PMID:42713910 | DOI:10.3322/caac.70100

Front Immunol. 2026 Aug 20;17:1919864. doi: 10.3389/fimmu.2026.1919864. eCollection 2026.

ABSTRACT

Cholangiocarcinoma is an aggressive biliary tract malignancy in which metastatic relapse and primary or acquired resistance to immunotherapy remain major causes of mortality. Although immune checkpoint inhibitors have improved first-line treatment for advanced biliary tract cancer, most patients do not achieve durable benefit, indicating that immune failure is not explained by a single checkpoint pathway. In this Review, we propose a spatial immune-regulatory continuum for cholangiocarcinoma dissemination. Most direct single-cell and spatial evidence currently derives from intrahepatic cholangiocarcinoma, and its applicability to perihilar and distal disease remains to be established. This continuum begins in the tumor core and invasive front, where malignant cells, cancer-associated fibroblasts, tumor-associated macrophages, endothelial and lymphatic cells, regulatory T cells, immature neutrophils and excluded or dysfunctional cytotoxic T cells form a pro-invasive ecosystem. It then extends through extracellular vesicles, soluble mediators and lymphovascular routes that may educate organotropic pre-metastatic niches. Finally, lymph node, lung, liver, peritoneal and bone microenvironments provide organ-specific extracellular matrix, myeloid and stromal programs that enable immune evasion and metastatic colonization. By integrating clinical evidence, multi-omics studies, single-cell and spatial transcriptomics, extracellular vesicle biology, pre-metastatic niche concepts and emerging therapeutic strategies, we argue that cholangiocarcinoma metastasis should be targeted before overt dissemination whenever possible. In this Review, "metastasis-intercepting immunotherapy" is used as an author-defined conceptual framework for strategies intended to prevent or disrupt the immune-stromal conditions that enable dissemination and colonization, rather than merely shrink established metastatic lesions. Metastasis-intercepting immunotherapy will likely require rational combinations that reprogram the invasive front, restore dendritic-cell-mediated antigen presentation, block tumor-stroma-myeloid circuits, disrupt EV-mediated communication that may contribute to niche formation and select patients using spatial biomarkers rather than bulk immune markers alone.

PMID:42694469 | PMC:PMC13539491 | DOI:10.3389/fimmu.2026.1919864

J Hazard Mater. 2026 Sep 15;516:143449. doi: 10.1016/j.jhazmat.2026.143449. Epub 2026 Aug 30.

ABSTRACT

The global incidence of ulcerative colitis (UC) has significantly increased in rapidly industrializing nations, with numerous studies highlighting environmental exposures, particularly nitrogen dioxide (NO₂), as potential contributors to disease susceptibility. However, the clinical implications and molecular mechanisms linking NO₂ exposure to UC susceptibility remain poorly understood. This study investigated the associations between NO₂ and UC by integrating multi-omics data. We identified a CD8⁺ T cell subpopulation with a distinct phenotype characterized by perforin production, which potentially exacerbated colonic inflammation related to NO₂ exposure. To validate this hypothesis, we established mouse models exposed to NO₂, confirming increased CD8⁺ T cell infiltration and elevated perforin secretion through immunofluorescent (IF) staining. Employing artificial intelligence techniques, we identified Cell Division Cycle 25B (CDC25B) as a gene of interest correlated with putative NO₂-related UC signatures. Finally, through molecular docking (MD) and molecular dynamics simulations (MDS), we identified ozanimod as one of several computationally nominated compounds associated with the CDC25B‑related network; however, none of these computational predictions were experimentally validated in the present study. Collectively, these findings suggest a correlative link between perforin or CD8⁺ T cell-associated colonic inflammation and NO₂-associated UC susceptibility, and nominate CDC25B as a candidate gene for further investigation.

PMID:42679583 | DOI:10.1016/j.jhazmat.2026.143449