Tertiary lymphoid structures (TLSs) are increasingly recognized as important components of the tumor immune microenvironment, yet their prognostic and immunological implications in clear cell renal cell carcinoma (ccRCC) remain incompletely characterized. In this study, we performed an integrated bioinformatic and translational analysis to investigate TLS-associated molecular features in ccRCC. Using TCGA-KIRC transcriptomic data, we identified three TLS-related molecular subtypes with distinct survival outcomes and immune microenvironment characteristics. Based on prognostic TLS-associated genes, we developed a four-gene TLS-derived score (CSF2, CXCL13, IL1R2, and SGPP2) that stratified patients into groups with significantly different overall survival. The TLS score remained an independent prognostic factor after adjustment for clinical variables. Interestingly, higher TLS scores were associated with increased immune infiltration but poorer survival outcomes, suggesting that TLS-associated transcriptional patterns may reflect heterogeneous immune functional states rather than uniformly effective antitumor immunity. Computational analyses indicated potential differences in predicted immunotherapy response and mutation landscapes between TLS score groups. Limited experimental validation using fresh ccRCC specimens supported the feasibility of TLS score assessment and provided preliminary histopathological context for TLS-associated immune features. Overall, this study proposes a TLS-derived transcriptional signature that may help capture immune heterogeneity in ccRCC and may provide a complementary framework for prognostic assessment. Further studies are required to validate its biological and clinical relevance.

Virus-like particles (VLPs) are spontaneously generated from viral capsid proteins. VLPs imitate genuine viruses visually and physiologically, but lack viral DNA. Various VLP designs provide structural and functional appeal. Spontaneous polymerization of viral capsid proteins may result in the formation of VLPs with geometrical symmetry, which are often icosahedral, spherical, or rod-like. Moreover, functionalized VLPs may precisely target cancer cells and recruit macrophages to destroy them. The ability to target tumors for therapeutic drug delivery through VLP-based delivery platforms in novel and intriguing aspects related to cancer treatment is the primary goal of VLP design. Cancer therapies require precise targeting of diagnostic or therapeutic elements to tumor cells while avoiding healthy cells and tissues. VLPs offer an innovative approach as site-specific drug delivery systems, reducing systemic toxicity and minimizing injury to healthy cells. Immunotherapy, which boosts the host's immune system, has fewer side effects. Cancer vaccines aim to induce an immune response that provides protection against tumor cells. Due to their naturally fitted particle size and repetitive structural order, VLPs may be employed as a vaccine without any adjuvant. Recombinant VLP structures can be enhanced by including antigenic epitopes of viruses or different disease-related antigens, and targeting peptides to the interior and exterior surfaces, making them potential tools for future immunizations with preventive and regenerative qualities. Additionally, VLP-based delivery strategies may enhance immunogenicity and provide a more effective and safer approach to managing solid cancers with fewer side effects compared to chemotherapy or radiation. However, the production of chimeric VLPs still faces challenges, such as the need for more reliable preclinical animal models and associated costs. Despite these obstacles, ongoing research will improve VLP-based technologies and increase their potential advantages. This review aims to provide basic information on VLPs and outline current studies on their use as drug and vaccine delivery systems in different cancers, highlighting their potential as a promising cancer treatment strategy. The key terms in the literature search-including drug delivery, gene therapy, multi-capsid VLPs, and virus-like particles (VLPs)-were searched in international databases, namely Web of Science, PubMed, and Scopus from 2003 to 2022.

Renal tubulocystic oncocytoma (RTO) is an exceptionally rare variant of renal oncocytoma (RO) with poorly understood genetic underpinnings. This study aimed to characterize the clinicopathological features and genomic landscape of RTO to enhance diagnostic precision and elucidate its molecular profile.

Whole-exome sequencing (WES) was performed on a pathologically confirmed case of RTO to identify somatic mutations. Bioinformatics filtering identified single-nucleotide variants (SNVs) and insertions/deletions (INDELs), which were screened against databases such as the Cancer Gene Census (CGC) to identify potential driver and predisposing genes. Findings were validated via Sanger sequencing. Immunohistochemistry (IHC) was utilized for diagnostic marker assessment and tumor microenvironment (TME) characterization. Furthermore, a literature-based analysis of reported RTO cases was conducted across multiple databases, including PubMed, Ovid, Google Scholar, EMBASE, and Scopus.

WES analysis identified 399 somatic SNVs and 91 INDELs, as well as mutations in 14 candidate predisposing genes and 27 candidate driver genes, including mutations in 3 predisposing genes (COL7A1, CSF3R, and MKL1) and 11 driver genes (ZFHX3, TSC2, NFATC2, TCF7L2, TLR4, RANBP17, ITK, NEB [Chr2:152499355], NUP214, FBN2, and NEB [Chr2:152544903]). Drug-target prediction and resistance analysis identified several variants with potential therapeutic relevance. IHC staining confirmed positive expression of CD117, EMA, and E-cadherin, supporting the differential diagnosis. TME profiling revealed an "immune-cold" phenotype characterized by low densities of CD4+, CD8+, and FOXP3+ T cells, CD19+ and CD20+ B cells, CD56+ and CD57+ NK cells, and CD163+ tumor-associated macrophages, alongside minimal checkpoint activity and focal fibroblast activation. A comparative analysis with eight previously reported cases further contextualized these clinicopathological and immunophenotypic findings.

This study provides a comprehensive genomic characterization of RTO. The integration of molecular profiling, histopathology, and literature-based comparison broadens the understanding of RTO's molecular and immunophenotypic landscape, providing a foundation for future hypothesis-driven research.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM often exhibits resistance to conventional apoptosis-inducing therapies, and its immunosuppressive microenvironment limits the efficacy of existing treatments. Ferroptosis is an iron-dependent, lipid peroxidation-driven form of cell death. The unique metabolic reprogramming in GBM, including dysregulated iron metabolism, abnormal lipid metabolism, and imbalanced antioxidant defenses, collectively determines the susceptibility of tumor cells to ferroptosis. There is a bidirectional regulatory relationship between ferroptosis and the tumor immune microenvironment (TIME). Ferroptosis can release damage-associated molecular patterns and activate dendritic cells, thereby enhancing antitumor immunity. Simultaneously, the functional state of immune cells directly influences the progression of ferroptosis. Targeting ferroptosis can enhance the efficacy of temozolomide (TMZ) and increase radiosensitivity. Nanodelivery systems can overcome blood-brain barrier limitations, enabling the co-delivery of ferroptosis inducers and immunomodulators. The combination of ferroptosis with immune checkpoint blockade can reverse the suppressive TIME. This review systematically summarizes the mechanisms by which ferroptosis regulates the suppressive TIME of GBM; the application of ferroptosis-targeting strategies (including ferroptosis inducers, immunotherapy, and targeted nanomaterials) in GBM treatment; and prospects for clinical translation. Targeting ferroptosis provides a new direction for modulating the suppressive TIME of GBM and developing novel therapeutic strategies for GBM.

Tumor-associated macrophages (TAMs) are known to facilitate cancer progression. However, the diversity of TAM subsets and their distinct roles in GC remain poorly understood. This study aimed to evaluate the impact of legumain (LGMN)⁺ macrophages on GC progression and clarify the underlying mechanisms of their roles.

We used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) analyses from public databases (GEO and TCGA) to systematically evaluate the clinical prognostic significance of LGMN and to characterize the remodeling of its associated signaling pathways. To investigate the role of LGMN in mouse GC (TAMs), we generated macrophage-specific LGMN conditional knockout mice, LGMN^flox/flox; Lyz2-Cre. Utilizing a combination of subcutaneous xenograft tumor models, primary cell isolation and culture, immunofluorescence staining, and tube formation assays, we systematically elucidated the regulatory function and underlying molecular mechanisms of LGMN⁺ macrophages in GC progression.

We found that LGMN⁺ macrophages are significantly enriched in GC tissues, and their high infiltration was significantly associated with poor outcomes. Additionally, scRNA-seq revealed that hypoxia and immune suppression pathways are enriched in LGMN⁺ macrophages. LGMN⁺ macrophages infiltration levels showed a significant positive correlation with the infiltration of regulatory T (Treg) cells and endothelial cells. Mechanistically, conditional knockout of LGMN in macrophages inhibits tumor growth by reprogramming TAMs toward an anti-tumor phenotype, reducing Treg cell infiltration, and enhancing the infiltration level of CD8⁺ T cells. Furthermore, LGMN knockout can inhibit tumor angiogenesis by downregulating VEGF-A expression.

LGMN⁺ macrophages drive GC progression by promoting tumor angiogenesis and establishing an immunosuppressive microenvironment. Therefore, targeting this TAM subset may represent a novel therapeutic strategy for GC.

The immunosuppressive tumor microenvironment (TME) is a major barrier to the efficacy of cancer immunotherapy. Tumor metabolic reprogramming, particularly aerobic glycolysis (the Warburg effect), drives lactate accumulation in the TIME. Beyond fueling tumor growth, lactate-derived lysine lactylation (Kla) has emerged as a pivotal epigenetic and post-translational modifier, directly coupling metabolic activity to the regulation of immune cell function and tumor cell resilience.

This review synthesizes current evidence to delineate how the glycolysis-lactylation axis orchestrates a multi-faceted immunosuppressive program and confers broad therapy resistance. We detail its mechanisms in: (1) Inhibiting antitumor immunity by driving M2 macrophage polarization, enhancing regulatory T cell (Treg) function, and promoting CD8⁺ T cell exhaustion; (2) Enhancing intrinsic tumor cell resistance through lactylation-mediated DNA damage repair and stemness maintenance; and (3) Directly undermining immunotherapy, notably by stabilizing programmed cell death 1 ligand 1 (PD-L1). We critically evaluate emerging therapeutic strategies that target this axis, including inhibitors of glycolytic enzymes, lactate transporters (MCTs), and lactylation writers/erasers, and their potential to synergize with established immunotherapies.

Targeting the lactate-lactylation signaling hub represents a promising metabolic-epigenetic strategy to dismantle tumor-driven immunosuppression and overcome therapeutic resistance, particularly resistance to immunotherapy. Although a substantial body of preclinical evidence, ranging from cancer cell line models to patient-derived xenografts, supporting the potential of targeting this axis, its clinical translation remains hindered by a gap in the evidence hierarchy, necessitating further validation through prospective clinical trials.

Acinetobacter baumannii is a leading cause of healthcare-associated infections in immunocompromised patients and frequently exhibits multidrug resistance. Cefiderocol, a siderophore cephalosporin, is among the few remaining therapeutic options for infections caused by carbapenem-resistant A. baumannii (CRAB); however, its activity may differ by clonal lineage and can be further compromised in the biofilm state. This study investigates genomic features and cefiderocol efficacy against planktonic and biofilm-associated forms of oncology-derived A. baumannii isolates.

Twenty-five non-duplicate, consecutive clinical isolates of A. baumannii from oncology patients underwent whole-genome sequencing and multilocus sequence typing. Cefiderocol activity was quantified in planktonic and biofilm-associated states using minimum bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC) assays.

Ten sequence types were identified, with the high-risk sequence type 2 (ST2) clone accounting for 56% (14/25) of isolates. ST2 strains showed significantly higher resistance to aminoglycosides, carbapenems, and fluoroquinolones than non-ST2 (NST) strains. The carbapenemase gene bla _OXA-23 was detected exclusively in ST2. Colistin and cefiderocol were the most active agents overall. ST2 strains showed higher cefiderocol MBC values than NST strains. However, avibactam significantly reduced cefiderocol MBC in ST2, consistent with class D β-lactamases activity. ST2 and NST isolates exhibited comparable distributions of iron acquisition genes and similar CAS-detected siderophore activity under the assay conditions tested. Cefiderocol activity was significantly reduced in biofilms relative to planktonic cells (median MBEC 2 µg/ml versus median MBC 0.5 µg/ml). NST exhibited higher MBEC/MBC ratios than ST2 isolates, indicating greater biofilm-associated tolerance to cefiderocol.

Collectively, these data associate the predominance of oncology-derived ST2 with bla _OXA-23 carriage and higher cefiderocol bactericidal thresholds and show that cefiderocol activity is consistently reduced in the biofilm state. Future studies integrating functional measures of iron acquisition and β-lactamase activity will be needed to define the determinants of cefiderocol efficacy across lineages and growth states.

Pulmonary complications remain a major challenge after esophagectomy for esophageal cancer. While rehabilitation interventions aligned with Enhanced Recovery After Surgery (ERAS) principles show promise, the term "rehabilitation" is often applied to highly variable approaches-from isolated breathing exercises to comprehensive multimodal programs-raising concerns about clinical interpretability and generalizability. This systematic review evaluates the effectiveness of structured perioperative rehabilitation, with emphasis on intervention comprehensiveness, timing, and implications for real-world implementation.

We systematically searched PubMed, CINAHL, Cochrane Library, Web of Science, CNKI, Wanfang, and CBM from inception to October 31, 2024. Of 37 included studies, only 12 delivered interventions integrating ≥2 core components (e.g., exercise plus nutrition or education). Due to high clinical and statistical heterogeneity (I² > 90% for most outcomes), we prioritized narrative synthesis and conducted meta-analyses only within homogeneous subgroups-particularly those delivering continuous care across both preoperative and postoperative periods. Outcomes included functional capacity (6-min walk distance), cardiopulmonary function, pneumonia incidence, length of hospital stay (LOS), and health-related quality of life (HRQoL).

Comprehensive perioperative rehabilitation (integrating prehabilitation and postoperative rehabilitation) was uniquely associated with a significant reduction in postoperative pneumonia [RR = 0.34, 95% CI (0.19, 0.61); p < 0.0001]. In contrast, the pooled effect across all rehabilitation interventions showed a modest but statistically significant benefit [RR = 0.70, 95% CI (0.52, 0.96); p = 0.02], suggesting that while even simplified protocols may confer some protection, maximal risk reduction requires continuous, multimodal support spanning the entire surgical trajectory. In contrast, prehabilitation alone achieved the greatest reduction in hospital length of stay [MD = -2.94 days, 95% CI (-5.50, -0.37)] and significantly improved FEV₁ (SMD = 0.60). Multimodal programs consistently enhanced health-related quality of life [SMD = 0.76, 95% CI (0.60, 0.92)] and functional capacity (6-min walk distance, SMD = 0.90). Single-component interventions (e.g., respiratory training alone) showed inconsistent or negligible effects. The current evidence base is predominantly derived from studies conducted in China, reflecting strong regional research momentum while highlighting the need to validate these findings in other healthcare contexts.

Multimodal, multi-phase rehabilitation may meaningfully improve short-term recovery after esophagectomy, but its benefits are outcome-specific and contingent on intervention design: pneumonia prevention requires integrated perioperative care, while reductions in resource use and improvements in baseline physiology are primarily driven by prehabilitation. The current literature suffers from conceptual dilution of "rehabilitation," methodological variability, and limited long-term data. To enhance public health impact, future efforts should focus on scalable, standardized delivery models-such as community-integrated or telehealth-supported pathways-that extend support beyond hospital discharge, particularly in resource-constrained settings.

PROSPERO registration number: CRD42024617815.

The safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for prevention of chemotherapy-induced neutropenia (CIN) in patients undergoing oral chemotherapy remain unclear. This study aimed to investigate the safety and efficacy of PEG-rhG-CSF as primary prophylaxis for CIN in gastrointestinal (GI) cancer patients receiving combination chemotherapy regimens that include oral chemotherapy agents.

This is a prospective, single-center, open-label, exploratory, non-randomized controlled study. GI cancer patients was treated with intravenous oxaliplatin (130mg/m² on day 1) combined with either oral capecitabine (1000mg/m²) or S-1 (an oral fluoropyrimidine combination of tegafur, gimeracil, and oteracil potassium; 40-60 mg) administered twice daily on days 1-14 of a 3-week cycle. The treatment group received subcutaneous injection of PEG-rhG-CSF (6mg) 24 hours after oxaliplatin, while the control group received no primary prophylaxis. The primary endpoint was safety, and secondary endpoints included the incidence of CIN.

Between March 2022 and January 2023, 49 patients were screened, and 43 patients who completed at least two treatment cycles were included in the final analysis (26 in treatment group and 17 in control group). The overall adverse events (AEs) did not differ statistically (93.8% vs 100.0%, p = 0.542). For grade ≥ 3 AEs, the incidence of neutropenia was significantly lower in the treatment group compared to the control group (3.1% vs 35.3%, p = 0.005). No significant differences were observed in the rates of grade ≥ 3 thrombocytopenia (6.3% vs 17.6%, p = 0.326) and leukopenia (3.1% vs 0.0%, p = 1.000). Grade≥2 CIN was significantly lower in the treatment group (25.0% vs. 76.5%, p < 0.001).

In GI cancer patients on oral agents, primary PEG-rhG-CSF prophylaxis was well-tolerated and reduced grade ≥2 CIN, though randomized studies are needed.

https://www.chictr.org.cn, identifier ChiCTR2100054854.

Reduced muscle mass and impaired composition have each been independently associated with worse outcomes in patients with cancer. However, emerging evidence suggests that reduced muscle strength-namely, dynapenia-may be particularly important for prognostication, as it is easier to assess in clinical practice compared to muscle mass. Importantly, muscle mass and composition-as assessed with computed tomography images-may not fully capture key physiological changes and/or reflect whole-body alterations, particularly in patients who remain within the normal range. We investigated the predictive power for mortality of low muscle mass and impaired composition, weight loss (WL) and low strength, as well as their combination, in a cohort of patients with cancer.

Baseline data on muscle mass and radiodensity (Hounsfield units [HU]) at the L3 level-assessed using computed tomography-along with 6-month unintentional WL (relevant if ≥ 10% of usual body weight) and muscle strength by handgrip were pooled for 477 patients with cancer (59.1% male, mean age 61.2 ± 12.8 years) from studies conducted in Brazil, Canada and Italy. Patients were categorized by sex and body mass index-specific cutoffs for low skeletal muscle mass index, low skeletal muscle radiodensity, WL ≥ 10% and low handgrip strength. Patients were followed for at least 12 months until death or censoring.

During a median follow-up of 43 months (IQR: 28-83), 188 patients died. Kaplan-Meier analysis showed no survival differences for low skeletal muscle index or low radiodensity, regardless of handgrip strength. Only WL ≥ 10% consistently identified patients with poorer prognosis, independently of low handgrip strength. Fully adjusted Cox's regression models showed an independent association only with WL (HR = 1.56 [95% CI: 1.12;2.16]; p = 0.008) and low handgrip strength (HR = 2.07 [95% CI: 1.47;2.92]; p < 0.001), as well as an increased risk for all low handgrip strength/%WL categories. Mortality risk increased across all low handgrip strength/%WL categories. Among the eight risk groups combining low skeletal muscle mass index, WL ≥ 10% and low handgrip strength, only those including WL ≥ 10% and low handgrip strength were significantly associated with higher mortality. Low skeletal muscle mass index contributed to a worse prognosis only when combined with both WL ≥ 10% and low handgrip strength. Similar results were observed when skeletal muscle radiodensity was used in replacement of skeletal muscle mass index.

In patients with cancer, muscle strength and WL were stronger survival predictors than muscle mass and composition, reinforcing their relevancy as easily assessed key markers of muscle health.