The liver immune microenvironment is a complex system regulated by the interaction between circulating immune cells and resident immune cell populations. In recent years, liver resident immune cells (LRICs) have received increasing attention as an important cell population for regulating liver pathology. These types of non-circulating liver cells have unique adaptability, not only meeting the metabolic needs of the liver but also maintaining its immune homeostasis. The advancement of high-throughput technology has enabled in-depth research on the unique origin, developmental pathways, and functional plasticity of LRICs. LRICs can initiate rapid, strong, and long-lasting tissue-specific immune responses to effectively curb disease progression. However, these powerful abilities may translate into pathogenic factors in specific situations: triggering tissue damage in the autoimmune environment and mediating graft rejection after liver transplantation. This article systematically reviews the current understanding of these key resident immune cell populations, details their multidimensional and often paradoxical mechanisms of action in a variety of major liver pathologies, and discusses the prospects of emerging therapeutic strategies for these key cell players.
Immune checkpoint blockade has fundamentally reshaped the therapeutic landscape of lung cancer. However, durable clinical benefits remain restricted to a subset of patients. Members of the tumor necrosis factor receptor superfamily (TNFRSF) and their ligands represent a highly versatile class of immune regulators governing T cell activation, immune cell crosstalk, and tumor microenvironment remodeling. Unlike classical immune checkpoints, TNFRSF signaling exhibits pronounced functional plasticity, displaying immunostimulatory or immunosuppressive effects depending on cellular context, spatial organization, and disease stage. This duality complicates the clinical translation of TNFRSF-targeted strategies, despite compelling preclinical evidence and their relevance in immune-related toxicities and inflammatory disorders. In this review, we synthesize recent advances in understanding the context-dependent roles of key TNFRSF axes in lung cancer, focusing on their contributions to immune activation and escape and therapeutic resistance. We further discuss emerging technologies and rational combination strategies that may enable more precise and effective exploitation of TNFRSF pathways, aiming to clarify the opportunities and limitations of TNFRSF-based immunotherapy in lung cancer.
ROS1-rearranged lung adenocarcinoma is a rare subset of non-small-cell lung cancer, typically occurring in young never-smokers. Its occurrence in very young men with a fluid-dominant presentation is unusual and may lead to diagnostic pitfalls. We herein report a case of ROS1-rearranged lung adenocarcinoma in a never-smoking man in his early 20s who presented with pericardial, pleural, and peritoneal effusion. The initial cytological assessment of the pericardial fluid, interpreted in the context of the patient's very young age, favored reactive mesothelial proliferation. Clusters with nuclear eccentricity and prominent nucleoli prompted the preparation of a cell block. Hematoxylin and eosin staining revealed cohesive nests, cords of tumor cells, and true gland-forming tubular structures with scattered mucin-containing cells. Immunohistochemistry confirmed primary lung adenocarcinoma, and a molecular analysis identified a ROS1 rearrangement. This case underscores the rarity of ROS1-rearranged adenocarcinoma in a very young never-smoking man, its atypical fluid-dominant manifestation, particularly pericardial effusion, and the importance of a systematic diagnostic approach that incorporates smear cytology, cell block, immunohistochemistry, and molecular testing, supported by multidisciplinary discussion to avoid a misdiagnosis and guide targeted therapy.
To explore the clinical value of prenatal ultrasound suggesting enhanced fetal renal echo, compare the genetic results and pregnancy outcomes, and provide reference for clinical consultation and prognostic evaluation. A total of 163 cases with enhanced fetal renal echo detected by ultrasound were collected. The ultrasound images and basic maternal data were analyzed, the genetic diagnosis results were compared, and the pregnancy outcomes were followed up. Among the 163 cases, 42 cases (25.77%) of genetic abnormalities were detected, including 24 cases (57.14%) of chromosomal abnormalities, among which 17q microdeletion accounted for the highest proportion. The differences in the detection rate of genetic abnormalities and the incidence of adverse pregnancy outcomes between the advanced age group and the non-advanced age group were statistically significant (p < .05). Enhanced fetal renal echo is closely related to genetic abnormalities, especially 17q abnormalities. When the pregnant woman is of advanced age or the fetus is complicated with other ultrasound abnormalities, the risk of genetic abnormalities increases, requiring focused screening and intervention.
Advanced gastroesophageal cancers often have poor survival rates even with chemotherapy. We aim to study the long-term safety and efficacy of combining PD-1/PD-L1 inhibitors with chemotherapy, incorporating biomarker analysis and recent Phase III trial data. Data from eight phase III trials (from inception to 2025, comprising 5668 patients) was combined in this PRISMA-guided meta-analysis. Overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and grade ≥3 adverse events were among the outcomes. Random-effects models were employed for statistical synthesis, and I2 was used to assess the heterogeneity. Cochrane RoB 2.0 was used to evaluate the risk of bias. Compared to chemotherapy alone, the combined regimen significantly improved overall survival (HR: 0.79; 95% CI: 0.75–0.83; p < .0001), progression-free survival (HR: 0.73; 95% CI: 0.68–0.78; p < .00001), and objective response rate (OR: 1.60; 95% CI: 1.44–1.78; p < .0001). The CPS ≥10 subgroups showed the greatest benefits (OS HR, 0.66; PFS HR, 0.63; p < .0001). Although manageable, grade ≥3 adverse events (OR, 1.37; 95% CI: 1.20–1.56) and immune-related toxicities (OR: 3.44; 95% CI: 2.91–4.08) were more common with ICIs. The OS advantage was greatest for MSI-high tumors (HR: 0.54; p < .04), but was not significant for esophageal cancers (HR: 0.88; p < .18). With long-lasting improvements in survival and manageable toxicity, PD-1/PD-L1 inhibitors in combination with chemotherapy constitute the first-line standard for advanced gastric/GEJ malignancies. Immune checkpoint inhibitors show a higher incidence of adverse events, and clinicians should balance efficacy against adverse event risk.
The purpose of this qualitative study was to understand the manifestations of occupational anxiety in young thyroid cancer survivors prior to their return to work and to explore coping strategies and essential support upon their return to work. Using purposive sampling, 13 young thyroid cancer survivors were selected for in-depth interviews from July to October 2023. Colaizzi's seven-step analysis method and NVivo software were used to analyze and organize the interview data. Three themes and 12 subthemes were summarized from the interview data: occupational anxiety caused by disease (fear of cancer recurrence, medication behavior anxiety, stigma of illness); manifestations of occupational anxiety (physical disruption, concerns about work intensity, dissatisfaction with the working environment, career disruption, career and job security disruption); and coping strategies (self-regulation, self-improvement, family support, peer support). Medical professionals should recognize the impact of occupational anxiety on young thyroid cancer survivors before returning to work. They should accurately identify and understand the causes, manifestations, and coping methods to alleviate survivors' occupational anxiety prior to their return to work. By establishing vocational guidance, they can improve survivors' cognition regarding the benefits of returning to work and reduce their occupational anxiety.