Non‑small cell lung cancer (NSCLC) is characterized by marked spatial immune heterogeneity, commonly manifested as immune‑desert, immune‑excluded and immune‑inflamed phenotypes. These phenotypes are closely associated with variable responses to immune checkpoint inhibitors (ICIs). Emerging evidence suggests that they are shaped not only by canonical immune pathways but also by mitochondrial processes that regulate immune priming, T‑cell trafficking and the maintenance of effector function. The present review summarizes how mitochondrial reactive oxygen species, mitochondrial DNA‑cGAS‑STING signaling, pathways mediated by tricarboxylic acid cycle metabolites, and non‑cell‑autonomous mitochondrial transfer may contribute to the establishment and maintenance of distinct spatial immune phenotypes in NSCLC. It is proposed that insufficient activation of innate immunity and impaired dendritic cell priming are particularly relevant to immune‑desert tumors, whereas chronic oxidative stress may reinforce barriers mediated by cancer‑associated fibroblasts (CAFs), transforming growth factor β, and the extracellular matrix in immune‑excluded tumors. By contrast, immune‑inflamed tumors may represent a state in which pre‑existing immune circuitry remains intact and tumor‑infiltrating lymphocytes retain greater mitochondrial fitness and metabolic resilience. The implications of these mechanisms for ICI sensitivity and cold‑to‑hot tumor conversion strategies were further discussed. Current evidence from human studies remains largely correlative, and prospective, spatially resolved functional studies are needed. Nevertheless, integrating mitochondrial biology with spatial immune architecture within a phenotype‑guided framework may generate testable hypotheses for future biomarker development and combination strategies.

Following the publication of the above article, a concerned reader has contacted the Editorial Office to draw attention to the fact that there appeared to be discrepancies between the numbers of patients reported with low‑ or high‑ZNF703 expression in Fig. 3 on p. 1074: Fig. 3A reported 70 patients with low ZNF703 expression and 68 patients with high expression; however, the stage‑stratified Kaplan‑Meier  curves showed the following: In Fig. 3B, stages I‑IIIA: 57 low‑expression and 20 high‑expression patients, and in Fig. 3C, stages IIIB‑IV: 20 low‑expression and 41 high‑expression patients (and so 70 vs. 68 patients in Fig. 3A, and 77 vs. 61 patients in Fig. 3B and C). In addition, the AJCC stage‑specific counts reported in Table I also showed internal inconsistencies in terms of the overall numbers of low‑ and high‑expression patients, and finally, an additional discrepancy was noted for the definition of the high expression group: The Materials and methods section stated that an immunohistochemical score of ≥6 was classified as high expression, whereas the Table I column heading defined high expression as '>6'. To clarify these apparent discrepancies, the authors should resolve the following: i) provide the actual numbers of low‑ and high‑expression patients in each AJCC stage group; ii) clarify whether the cutoff used for the Kaplan‑Meier analyses was ≥6 or >6; iii) provide the exact patient numbers used to generate Fig. 3A, B and C; and iv) clarify whether the counts, totals and percentages in Table I require correction. Finally, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that, regarding the wound healing assay data shown in Fig. 6A on p. 1076, the '24 h / Control' and '24 h / NC siRNA' panels showed an overlapping section of data, such that data which were intended to show the results of experiments performed under different conditions had apparently been derived from the same original source. The authors have been contacted by the Editorial Office to offer an explanation for the apparent anomalies in the description of the data, and the incorrect assembly of data in Fig. 6, in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of this potential issue concerning the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 32: 1071‑1077, 2014; DOI: 10.3892/or.2014.3313].

Bone metastases are common in advanced solid tumors and are clinically important not only because they cause skeletal-related events, including bone pain, pathological fractures, and spinal cord compression, but also because they may influence responses to immune checkpoint inhibitors (ICIs). Clinical evidence has consistently associated bone metastases with poorer survival after ICI treatment. Although some studies suggest that the relative benefit of ICIs may be reduced in patients with bone metastases, most available evidence is retrospective and lacks adequate treatment-interaction testing. This apparent reduction in benefit therefore cannot be clearly distinguished from adverse baseline prognosis, greater disease burden, or confounding related to concomitant treatments. Lesion-level studies further suggest that bone and nonbone lesions may follow discordant response trajectories. Assessment of bone-lesion response is complicated by the limited measurability of bone-only lesions under RECIST 1.1 and by treatment-related sclerosis, bone flare, and mixed responses. Mechanistically, bone metastases may establish a site-specific osteoimmune niche in which abnormal bone remodeling, vascular and stromal reorganization, myeloid immunosuppression, and impaired T-cell infiltration and effector function jointly constrain local antitumor immunity. RANKL inhibition and bone-directed radiotherapy are clinically available and may have immunomodulatory effects, but current evidence does not establish that either approach consistently enhances the antitumor activity of ICIs beyond skeletal protection or local control. Most other microenvironment-directed strategies remain at the preclinical or early translational stage. Future studies should distinguish bone-lesion antitumor response from systemic disease control and skeletal clinical outcomes. Prespecified treatment-interaction analyses, longitudinal multimodal imaging, paired sampling of bone and nonbone lesions, and mechanism-embedded clinical trials will be required to determine whether specific osteoimmune niche states can guide patient selection and combination therapy.

DICER1-related tumor predisposition is a rare hereditary tumor predisposition disorder characterized by autosomal dominant inheritance, reduced penetrance, and variable expressivity. This study is aimed at describing the clinical and molecular spectrum of DICER1-related tumor predisposition in an Argentine pediatric cohort.

Seventeen unrelated patients with DICER1-related tumor predisposition and 54 relatives were evaluated at "Prof. Dr. J. P. Garrahan" Pediatric Hospital (Buenos Aires, Argentina) between 2014 and 2024. Germline and somatic DICER1 variants were analyzed using Sanger or next-generation sequencing. Functional assays were performed for selected intronic variants. Three samples of poorly differentiated thyroid carcinoma were also included.

Sixteen distinct germline variants were identified in the 17 index cases, including 12 novel alterations (75%). One quarter of the variants were de novo. Thyroid involvement, particularly multinodular goiter and papillary thyroid carcinoma, was the most common presentation and frequently coexisted with ovarian Sertoli-Leydig cell tumors or embryonal rhabdomyosarcoma. Two novel intronic variants were confirmed to affect splicing by RT-PCR. Somatic "hotspot" mutations in exons 24-25 (RNase IIIb domain) were detected in most tumors, consistent with the two-hit model. The identification of asymptomatic carriers enabled early surveillance and preventive interventions.

This study expands the molecular spectrum of germline DICER1 variants, reinforces the predominance of thyroid involvement, and highlights the value of molecular testing for diagnosis, genetic counseling, and early intervention. Ethical considerations regarding surveillance and management of asymptomatic carriers remain an important area in need of future guidance.

Older women undergoing cancer surgery commonly enter the perioperative period with overlapping frailty, malnutrition, sarcopenia, obesity, multimorbidity, and treatment-related symptoms. These vulnerabilities reduce physiologic reserve and amplify the catabolic response to surgery, increasing the risk of complications, functional decline, delayed adjuvant treatment, and persistent nutritional impairment. Nutrition-oriented perioperative nursing provides a practical framework for translating frailty assessment and cancer nutrition guidance into coordinated care before surgery, during enhanced recovery, and after discharge. This Mini Review examines the frailty-malnutrition-surgical stress axis in older women with breast, gynecologic, thoracic, and other cancers requiring surgery. We propose an integrated two-step approach in which brief frailty and nutrition screening triggers multidimensional assessment, dietitian referral, symptom management, protein-energy support, and multimodal pre-habilitation. Within enhanced recovery pathways, nurses can protect nutritional intake by limiting unnecessary fasting, supporting individualized carbohydrate use, preventing postoperative nausea and vomiting, promoting early protein-containing oral feeding, and coordinating early mobilization. Continued reassessment after discharge is required because muscle loss, appetite disturbance, and treatment-related nutritional problems may persist into adjuvant therapy and survivorship. Current evidence supports integrated screening and multimodal care, but women-specific trials in geriatric oncology remain limited. Future studies should evaluate nurse-led implementation using functional, nutritional, treatment-continuity, and patient-reported outcomes rather than length of stay alone.

Remodeling of tumor-draining lymph nodes (tdLNs) can precede overt nodal metastasis and has emerged as a determinant of immune checkpoint blockade (ICB) responsiveness. Sustained lymphatic delivery of tumor-derived antigens, extracellular vesicles, cytokines, and metabolites perturbs stromal and vascular programs, including lymphatic expansion, high endothelial venule dysfunction, and disruption of fibroblastic reticular cell (FRC) networks, with downstream impairment of antigen presentation and T-cell priming. Metabolites such as lactate and adenosine further promote tolerogenic antigen-presenting cell states and increase the activation requirements of tumor-reactive T cells. These changes are predicted to reduce the availability of TCF1⁺ progenitor-exhausted CD8⁺ T cells (Tpex), an ICB-responsive reservoir that sustains clonal expansion during PD-1/PD-L1 blockade. The Review links tdLN structural, cellular, and metabolic remodeling to ICB response and resistance, highlights reinforcement of regulatory circuits after metastatic colonization, and discusses translational strategies that incorporate tdLN functional state into therapeutic design, including restoration of type 1 conventional DC (cDC1) competence, metabolic co-targeting, neoadjuvant sequencing, adoptive use of tdLN-derived T cells, and biomarker-guided planning of local therapies.

Immune checkpoint inhibitors (ICIs) are a cornerstone of therapy for advanced non-small cell lung cancer (NSCLC). Elderly patients remain underrepresented in clinical trials, and the prognostic significance of immune-related adverse events (irAEs)-including their cumulative burden-across age groups is not fully defined. This study evaluated age-related differences in clinical characteristics, treatment patterns, irAEs, and outcomes in patients with stage IV NSCLC.

This retrospective multicenter study included 452 patients with metastatic NSCLC treated with ICIs, with or without chemotherapy. Patients were stratified by age (<75 vs. ≥75 years). irAEs were analyzed both by occurrence (yes vs. no) and by burden (≤2 vs. >2 different irAE types). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared across age and irAE subgroups.

Among the 452 patients, 344 (76.1%) were <75 years old and 108 (23.9%) were of ages ≥75 years. Baseline characteristics, including histology and PD-L1 expression, were comparable between age groups. Older patients were more frequently treated with immunotherapy alone or dual immunotherapy and less often received chemo-immunotherapy (p = 0.024). The distribution of irAEs differed significantly by age (p < 0.001), with patients ≥75 years of age experiencing a higher frequency of >2 irAE types. The median PFS and OS for the entire cohort were 12.0 and 15.0 months, respectively. While PFS was similar between age groups, OS was significantly shorter in patients of age ≥75 years (p = 0.008). Across both age groups, the occurrence of irAEs was associated with significantly improved PFS and OS. A higher irAE burden (>2 different types) was associated with numerically longer survival in both younger and older patients.

ICIs are effective in elderly patients with advanced NSCLC. The presence of irAEs-and potentially a higher irAE burden-is associated with improved survival outcomes regardless of age, supporting irAEs as a clinically meaningful biomarker of immunotherapy benefit, including in patients ≥75 years of age.

The spatial tumor immune microenvironment (TIME) determines therapy response in colorectal cancer liver metastases (CRLM). To overcome biopsy sampling bias, this study investigates multimodal macroscopic image fractal dynamics to non-invasively map immune physical barriers and metabolic states, constructing a multi-scale immune-radiomics joint score (IRJS) for robust prognostic stratification and exploratory assessment of treatment resistance.

This dual-center observational study enrolled 270 CRLM patients with dual-modality imaging (contrast-enhanced magnetic resonance imaging, CE-MRI, 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed-tomography, ¹⁸F-FDG PET/CT) and digital spatial pathology. Patients were spatiotemporally divided into training (n=150), prospective temporal validation (n=45), and external validation (n=75) cohorts. Structural (FD_MRI) and metabolic (FD_PET) fractal dimensions were combined with the systemic immune-inflammation index (SII) and KRAS status to build the IRJS using XGBoost, utilizing the SHAP framework to evaluate mapping mechanisms.

FD_MRI positively correlated with α-SMA⁺ pro-fibrotic stromal density (r = 0.684), which may reflect the mechanical barrier excluding CD8⁺ T cells. FD_PET showed a significant association with core hypoxia (HIF-1α) and systemic immune exhaustion. IRJS robustly identified the immune-inflamed phenotype across training, temporal, and external validation cohorts (AUCs: 0.921, 0.886, 0.862, respectively). The IRJS-identified inflamed phenotype was an independent protective factor for overall survival (HR = 0.31, P < 0.001). Furthermore, IRJS demonstrated significant clinical net reclassification improvement (NRI = 0.384, P < 0.001) and net clinical benefit in decision curve analysis.

Dual-modal fractal dynamics provide non-invasive surrogate markers for mechanical constraints and metabolic exhaustion in CRLM. The IRJS model enables robust spatiotemporal assessment of immune evasion, offering multidisciplinary teams a potential framework to explore non-invasive biopsy decisions, prognostic stratification, and provide exploratory insights into potential immunotherapy resistance.

To explore the latent class characteristics of psychological resilience in patients with brain glioma, identify influencing factors, and examine differences in psychosocial indicators across latent classes.

A total of 224 patients with brain glioma hospitalized in the Department of Neurosurgery of a tertiary Grade A hospital between January 2023 and December 2024 were selected using convenience sampling. Psychological resilience, anxiety and depression, quality of life, and perceived social support were assessed using the 14-item Resilience Scale (RS-14), Hospital Anxiety and Depression Scale (HADS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and Perceived Social Support Scale (PSSS), respectively. Latent class models were constructed using Mplus 8.3, and univariate analysis and multivariate logistic regression were performed using SPSS 26.0.

Psychological resilience in patients with brain glioma was classified into three latent classes: a low-level profile (25.0%), a moderate-level variable profile (32.6%), and a high-level profile (42.4%). Significant differences were observed among the classes in anxiety (p < 0.001), depression (p = 0.002), symptom burden (p = 0.018), global health status (p = 0.003), and family support (p = 0.018). Multivariate logistic regression analysis showed that age ≥60 years (p = 0.019), WHO grade III-IV glioma (p = 0.004), disease recurrence (p = 0.013), higher anxiety score (p < 0.001), and higher depression score (p = 0.032) were associated with a greater likelihood of belonging to a lower psychological resilience class, whereas college education or above (p = 0.027), monthly household income ≥10,000 RMB (p = 0.016), better global health status (p = 0.013), and higher family support (p = 0.018) were associated with a greater likelihood of belonging to a higher psychological resilience class.

Within this clinical sample, psychological resilience in patients with brain glioma exhibited distinct heterogeneous stratification, with systematic differences in psychological status and social support across latent classes. The identification of resilience subtypes may help clinicians recognize patients who require further psychosocial assessment and may inform the development of stratified psychological support strategies. However, prospective longitudinal and interventional studies are needed to determine whether subtype-based interventions can improve psychological adaptation.

To characterize the association between reported human papillomavirus (HPV) genotype detection patterns with cervical lesion burden and to assess variation by region, year, age, reported prior screening history, and diagnostic category in a province-wide cervical cancer screening program in Guangdong, China.

We conducted a screening program-based cross-sectional study using 1,291,583 individual-level screening records collected during 2017-2022. Aggregate lesion data from Guangzhou, Dongguan, and Zhongshan supplemented city- and region-level lesion analyses. Genotype-specific analyses included 1,244,766 records with genotype-level results. Joinpoint regression and adjusted generalized linear models were used to assess temporal and age-related patterns. Sensitivity analyses retained only the earliest eligible record for each identifiable woman.

High-risk HPV was detected in 63,004 records (4.88%). Low-grade squamous intraepithelial lesions (LSIL), high-grade/microinvasive cervical lesions, and cervical cancer were recorded in 11,106 (0.86%), 6,633 (0.51%), and 382 (0.03%) records, respectively. The cities with the highest pooled proportions differed across lesion categories. Overall low-risk and high-risk HPV positivity showed significant positive annual percentage changes of 19.21 and 8.05%, respectively, whereas no individual high-risk genotype changed significantly. High-risk HPV positivity was highest in Northern Guangdong (5.6%), and HPV16 was the most frequently reported genotype in all four regions. Compared with participants aged <45 years, those aged ≥65 years had adjusted relative risks of 1.52 (95% CI, 1.22-1.91) for high-grade/microinvasive cervical lesions, 5.02 (2.43-10.35) for cervical cancer, and 1.51 (1.39-1.63) for high-risk HPV positivity. Age-related differences in severe lesions were more evident among records with no prior screening reported. The detection proportion of HPV16 increased from 28.6% in LSIL to 50.0% in high-grade/microinvasive cervical lesions and 69.3% in cervical cancer. HPV18 ranked second in cancer (18.3%), whereas HPV52 and HPV58 were more frequent in LSIL and high-grade/microinvasive lesions.

This province-wide screening study linked reported HPV genotype patterns with cervical lesion burden and identified uneven disease burden across Guangdong, a higher burden of severe cervical lesions among older participants with no prior screening reported, and distinct genotype-specific detection patterns across lesion grades. These findings support locally adapted screening and follow-up strategies that prioritize high-burden regions, under-screened older women, and genotype-informed follow-up of HPV-positive women.