PD-1/PD-L1 blockade can produce durable tumor control, yet primary, adaptive, and acquired resistance remain common. Existing accounts often catalogue resistance by cellular compartment, obscuring the coordinated nature of tumor adaptation. Here, we introduce immune-pressure redistribution as a treatment-oriented framework that complements cancer immunoediting by asking where therapeutic immune pressure is diverted after checkpoint release. Resistance is organized into three coupled routes: transfer into tumor-intrinsic escape through antigen-presentation loss, interferon-response defects, oncogenic rewiring, and lineage plasticity; weakening through defective priming, terminal T-cell differentiation, compensatory checkpoints, metabolic constraint, and chronic cytokine signaling; and unloading into stromal, vascular, myeloid, regulatory, microbial, and systemic host compartments. We integrate clinically validated mechanisms with emerging evidence, including the temporal duality of interferon-JAK signaling, the role of tumor-draining lymph nodes in sustaining progenitor-exhausted T cells, and the limited translation of TIGIT, IDO1, TGF-β, and CSF-1R targeting. We further propose a biomarker-guided strategy that combines tumor visibility, immune-cell state, spatial architecture, systemic inflammation, and early treatment dynamics to identify the dominant resistance topology. This framework supports topology-matched combinations and adaptive sequencing rather than uniform escalation, with the aim of restoring productive immune pressure while limiting compensatory escape and toxicity.

Among breast cancer (BC) survivors, overweight and obesity increase the risk of recurrence, underscoring the importance of dietary strategies for weight management. The Mediterranean diet (MD) can promote weight loss and reduce lipid levels. Analyzing alterations at the lipid species level can provide more detailed insights into the metabolic benefits associated with the MD. This study aimed to explore lipid remodeling associated with MD adherence in BC survivors through comprehensive lipidomic analysis.

This exploratory ancillary study was conducted as non-randomized, non-controlled pre-post intervention analysis of serum samples collected before and after an 8-week MD intervention from 12 overweight or obese BC survivors. Fasting paired serum samples (n = 24) were used to profile lipid species using ultra-high-performance liquid chromatography-tandem mass spectrometry in both positive and negative ionization modes. Multivariate and correlation analyses were used to assess overall lipidomic alterations. Participants were further classified into maintainer or improver subgroups based on changes in their Mediterranean diet score (MDS), and subgroup-specific lipidomic responses to the MD intervention were examined.

Participants showed significant reductions in body weight, waist circumference, and clinical triglyceride levels, along with increased quantitative insulin sensitivity check index and MDS following the MD intervention. Forty-three putative lipid species were identified, predominantly characterized by reductions in triacylglycerols (TGs) enriched with saturated fatty acids. TG 16:0_18:0_18:0 and TG 16:0_18:1_24:0 exhibited strong negative correlations with MDS and positive correlations with insulin resistance markers. Significant lipid remodeling was observed only in the maintainer group.

In this exploratory study, adherence to an 8-week MD was associated with changes in body composition, metabolic markers, and the serum lipidomic profile in overweight and obese BC survivors. These findings provide preliminary evidence that MD adherence may be associated with lipidomic and metabolic changes in BC survivors, warranting confirmation in larger, controlled studies.

http://clinicaltrials.gov , NCT03581630.

Acute lymphoblastic leukemia (ALL) is a common type of acute leukemia and is essentially a malignant clonal proliferative disorder of hematopoietic stem cells. Currently, the widespread application of high-dose chemotherapy combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) has significantly improved patient survival and has become the most effective therapeutic strategy for ALL. However, relapse remains a major challenge after transplantation. Most relapses occur in the bone marrow, whereas extramedullary relapse is relatively uncommon, and relapse involving the female reproductive system is extremely rare. Herein, we report a case of ALL with uterine and ovarian relapse after allo-HSCT. Extramedullary relapse was confirmed by pelvic mass biopsy. The patient subsequently received combined treatment with chemotherapy, radiotherapy, and chimeric antigen receptor T‑cell (CAR‑T) immunotherapy, resulting in complete regression of the uterine and ovarian lesions and achieving clinical remission. It should be noted that relapse of acute leukemia in the reproductive system after transplantation can be easily misdiagnosed as a primary malignancy of the reproductive system. Therefore, accurate differentiation between primary and secondary tumors and early initiation of effective treatment are essential. In clinical practice, diagnostic accuracy should be improved by integrating the patient's clinical history with magnetic resonance imaging (MRI) findings, thereby avoiding unnecessary surgical trauma and improving long‑term prognosis.

Dysregulation of mitophagy contributes to the initiation and progression of hepatocellular carcinoma (HCC). Nuclear protein localization 4 homolog (NPLOC4) is an essential protein involved in various cellular processes and has been implicated in multiple cancers. Recent studies have suggested that NPLOC4 participates in the regulation of mitophagy; however, its role in HCC remains unclear. This study aims to investigate the role of NPLOC4 in mitophagy and its underlying regulatory mechanisms in HCC.

RNA sequencing data from the GSE277232 and GSE251942 datasets obtained from the Gene Expression Omnibus (GEO) database were analyzed together with mitophagy-related genes collected from the GeneCards database to identify differentially expressed mitophagy-related genes in HCC. NPLOC4 expression was further analyzed and validated by Western blotting. Small interfering RNA (siRNA)-mediated knockdown of NPLOC4 was performed in HCC cells for functional loss-of-function assays. Mitophagy levels were evaluated by analyzing the expression of mitophagy-related proteins, transmission electron microscopy, and immunofluorescence staining.

Bioinformatics analysis identified NPLOC4 as a key differentially expressed mitophagy-related gene. NPLOC4 was significantly upregulated in HCC tissues and was associated with poor clinical prognosis (all P<0.05). Knockdown of NPLOC4 inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis (all P<0.05). In addition, NPLOC4 knockdown suppressed mitophagy and the Wnt/β-catenin signaling pathway in HCC cells (all P<0.05). Treatment with the Wnt agonist BML-284 abolished the inhibitory effect of NPLOC4 knockdown on mitophagy (P<0.05), indicating that NPLOC4 regulates mitophagy through activation of the Wnt/β-catenin pathway. Furthermore, treatment with the mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP) reversed the inhibitory effects of NPLOC4 knockdown on HCC cell proliferation, migration, and invasion (all P<0.05), suggesting that NPLOC4 silencing suppresses HCC progression by regulating mitophagy.

NPLOC4 is highly expressed in HCC. Downregulation of NPLOC4 inhibits activation of the Wnt/β-catenin signaling pathway, thereby inhibiting mitophagy and ultimately inhibiting HCC cell proliferation, migration, and invasion. These findings suggest that NPLOC4 may serve as a potential biomarker and therapeutic target for HCC.

Recent trials support omitting axillary lymph node dissection (ALND) in selected sentinel node-positive patients, but those with preoperative biopsy-proven nodal metastasis remain underrepresented. We characterized axillary nodal burden and its preoperative predictors.

We retrospectively studied patients with cT1-3 breast cancer and biopsy-proven axillary metastasis who underwent upfront ALND between 2008 and 2023 with at least one positive node. Nodal burden was classified as limited (1-2 positive nodes) or extensive (≥3). Multivariable logistic regression identified predictors.

Among 1671 patients (median 21 nodes retrieved), 662 (39.6%) had limited and 1009 (60.4%) had extensive nodal burden. Suspicious node count on axillary ultrasound (AUS) was independently associated with extensive burden (two nodes: OR 2.26, 95% CI 1.64-3.12; ≥3 nodes: OR 2.08, 1.67-2.59; both p < 0.001), as was higher clinical T stage (cT2: OR 1.35, p = 0.009; cT3: OR 1.57, p = 0.008). Extensive burden ranged from 41.0% (cT1, one suspicious node) to 75.0% (cT3, two suspicious nodes). The AUS ≥3 and AUS 2 groups did not differ for ≥3 positive nodes but differed for ≥10 positive nodes (24.8% vs. 14.0%). Among 574 patients with a non-palpable axilla, AUS remained associated with extensive burden whereas clinical T stage did not.

Extensive nodal burden was common yet heterogeneous. AUS suspicious node count and clinical T stage were associated with extensive disease, but discrimination was modest. These findings do not support uniform omission of ALND and require prospective validation.

This study aimed to examine sexual quality of life (SQoL) and its associated factors among women with endometrial cancer, including menopausal symptoms, body image, sexual knowledge, and sexual function.

A cross-sectional observational study was conducted. A total of 113 women with endometrial cancer were recruited using convenience sampling. Data were collected through electronic questionnaires assessing demographic and clinical characteristics and key study variables. Hierarchical multiple regression analysis was performed to identify significant predictors of SQoL. The study was reported in accordance with the STROBE checklist for cross-sectional studies.

The mean SQoL score was 68.86 (SD = 20.59), with 37.2% of participants reporting low to moderate levels. Significant factors associated with SQoL included body mass index (β = -0.17), receipt of radiotherapy (β = -0.28), menopausal symptoms (β = -0.20), body image distress (β = -0.26), and sexual function (β = 0.38). The final model explained 46% of the variance (p < 0.001), with sexual function emerging as the strongest predictor.

SQoL among endometrial cancer survivors was associated with physiological, psychological, and functional factors. Sexual function showed the strongest association with SQoL, whereas receipt of radiotherapy and greater body image distress were associated with poorer SQoL. These findings highlight the importance of comprehensive survivorship care that includes routine assessment of sexual function, symptom management, body image support, and sexual rehabilitation. An integrated, multidisciplinary approach may help address the complex physical, psychological, and relational factors associated with sexual quality of life among endometrial cancer survivors.

To examine the perceived need, acceptability and anticipated feasibility of the nurse-led telephone follow-up care (NLTFC) approach as an adjunct to specialist-led breast cancer follow-up in India from the perspectives of survivors and healthcare professionals.

A convergent, qualitatively driven mixed methods study (QUAL + quan). Semi-structured interviews were conducted with 21 survivors and 27 healthcare professionals (19 nurses, 8 doctors). Surveys were completed by 120 survivors and 112 healthcare professionals (96 nurses, 16 doctors). Qualitative data were analysed using reflexive thematic analysis, and quantitative data were summarised using descriptive statistics and exploratory Fisher's exact tests. Findings were integrated and reported through narrative weaving and a joint display.

NLTFC received high survey-based support from survivors (99%), nurses (98%) and doctors (94%), with no statistically significant differences between nurses and doctors across the six perception statements. Participants perceived that NLTFC could improve accessibility, care coordination, psychosocial support and survivor empowerment while reducing travel, waiting times and financial burden. Despite the strong support, interviews identified concerns about clinical safety, nurses' preparedness and professional role boundaries. Structured follow-up plans, specialised oncology training, clearly delineated roles and multidisciplinary oversight were considered necessary for implementation.

NLTFC was perceived as an acceptable adjunct to specialist-led follow-up with potential to strengthen supportive care and redistribute specialist workload. The findings demonstrate anticipated rather than operational feasibility. Safe delivery would require formal clinical governance and investment in advanced oncology nursing roles. Prospective evaluation is required to assess feasibility, clinical safety, effectiveness and sustainability in India.

Nanomedicine has broad prospects in tumor diagnosis and treatment, but its clinical translation has long been limited by targeted delivery efficiency. The heterogeneity of the tumor microenvironment is like a "sea fog" that hinders precision medicine. This makes it difficult for traditional active targeting that relies on natural targets to achieve precise delivery. For this difficulty, this review summarizes the constraints of tumor microenvironment heterogeneity on nanomaterials in terms of time and space. Pre-targeting strategies enhance delivery efficiency by constructing an "artificial lighthouse." According to the source of the target and the mode of specific binding, this review divides pre-targeting strategies into two categories: biomolecular recognition-mediated and bioorthogonal click chemistry-mediated. On this basis, this review comprehensively introduces recent progress in pre-targeting-enabled nanomedicine in body fluid-based detection, in vivo imaging, and multi-therapies. Furthermore, this review is the first to summarize the synergistic mechanisms of pre-targeting with prodrugs, insitu self-assembly, and dual-targeting strategies. This review systematically summarizes the complete framework of pre-targeting strategies, from mechanisms and classifications to applications and expansions. It aims to provide inspiration for the development of nanomedicine in the field of oncology for effective cancer diagnosis and treatment.

Colorectal cancer (CRC) exhibits intrinsic resistance to conventional therapeutic regimens. By integrating single-cell and bulk transcriptomic data from CRC cohorts, we demonstrate that proliferative capacity alone constitutes an inadequate prognostic predictor. Instead, an immunosuppressive tumor microenvironment (TME) emerges as the dominant driver of disease progression. Galectin-1 (LGALS1), highly upregulated in metastatic CRC, correlates with robust infiltration of regulatory T cells (Tregs) and M2 macrophages to facilitate immune evasion and poor clinical outcomes, thereby serving as a promising therapeutic target for anti-tumor immunotherapy. The stromal barrier mediated by cancer-associated fibroblasts (CAFs) restricts intratumoral penetration of antitumor agents and diminishes therapeutic efficacy. To overcome this physical barrier, we constructed a CAF extracellular vesicle-based co-delivery platform termed CEV@Comb, encapsulating the LGALS1 inhibitor OTX008 and 5-fluorouracil (5-FU). CEV@Comb selectively accumulates in tumors, suppresses growth in vitro and in vivo, and remodels the immunosuppressive TME by boosting M1 macrophages and cytotoxic CD8⁺ T cells while reducing intratumoral Tregs. Combination therapy with CEV@Comb and anti‑programmed death‑1 antibody (αPD-1) further amplifies anti-tumor immunity in the Apc^-/-, Kras^G12D, Trp53^-/-, Smad4^-/-(AKPS) CRC mouse model. This study identifies LGALS1 as a core immunosuppressive mediator and provides an innovative chemoimmunotherapeutic strategy to improve clinical outcomes for patients with advanced CRC.

Oncogenic viral pathogens, such as human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis B and C viruses (HBV, HCV), and Kaposi's sarcoma-associated herpesvirus (KSHV), are involved in a significant proportion of human cancers worldwide. While genetic and epigenetic mechanisms underlying viral oncogenesis have been thoroughly investigated, emerging evidence underscores a critical role for epitranscriptomic regulation in virus-host interactions and their clinical consequences. RNA modifications such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ) dynamically modulate RNA stability, translation, and immune recognition, thereby regulating viral replication and persistence. The present review describes current knowledge on the epitranscriptomic landscape of oncogenic viral pathogens and its functional implications. This review discusses how viral and host transcripts are selectively modified by cellular writers, erasers, and readers, shaping key stages of the viral life cycle, including replication, latency, and reactivation. Particular emphasis is placed on the role of RNA modifications in maintaining chronic infection and promoting tumourigenesis through the regulation of oncogenic pathways, cell proliferation, and apoptosis. Additionally, the present review examines how epitranscriptomic marks contribute to immune evasion by altering innate immune sensing and interferon responses. Finally, it explores the therapeutic potential of targeting epitranscriptomic machinery, highlighting recent advances in small-molecule inhibitors and the challenges associated with specificity and off-target effects. A deeper understanding of epitranscriptomic regulation in oncogenic viruses may reveal novel biomarkers and therapeutic strategies for virus-linked malignancies.