Accurate assessment of PD-L1 expression is crucial for therapeutic decision-making in esophageal, esophago-gastric junction, and gastric cancers, where immune checkpoint inhibitors have become integral to first-line treatment in selected patients. This review provides an updated, practice-oriented summary on PD-L1 immunohistochemistry evaluation, with emphasis on the emerging Tumor Area Positivity (TAP) scoring system together with established Combined Positive Score (CPS) and Tumor Proportion Score. First, we examine the clinical relevance and use in clinical trials of each scoring method, and the pre-analytical and analytical variables influencing PD-L1 interpretation. Then, we address advantages and disadvantages of each scoring system, including a thorough analysis and pictorial interpretation guide of the recently introduced TAP score. Indeed, thanks to a visual-estimation-based assessment of PD-L1 expression, TAP has improved reproducibility and reduced scoring time, but large-scale validation is ongoing and certain interpretive challenges remain. Finally, we propose a standardized reporting template to enhance consistency in diagnostic practice, together with our perspective on future improvements and challenges of PD-L1 assessment.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with pulmonary involvement is a rare, indolent lymphoma with no standard treatment approaches.

This study is aimed at evaluating the relationship between preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) findings and histopathological necrosis rates following chemotherapy in patients diagnosed with osteosarcoma (OST) and Ewing sarcoma (EWS).

Anastomotic leakage is a major complication following laparoscopic low anterior resection in patients with low rectal cancer. This study investigated the preventive effects of three intraoperative techniques, including the preservation of the left colic artery, reinforcement suturing, and transanal decompression tube placement. A total of 88 patients undergoing laparoscopic rectal cancer surgery were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to assess the associations between these interventions and the occurrence of anastomotic leakage. The overall anastomotic leakage rate was 7.95%. Left colic artery preservation, reinforcement suturing, and transanal decompression tube placement each showed a lower anastomotic leakage incidence (5.3%, 6.3%, and 7.4%, respectively) compared with nonapplication. The combined use of all three measures resulted in zero anastomotic leakage. Multivariate analysis confirmed a consistent protective trend, with left colic artery preservation demonstrating the strongest effect. Preserving the left colic artery, reinforcing the anastomosis, and reducing intraluminal pressure act synergistically to reduce the risk of anastomotic leakage. Their integrated use may offer an effective strategy to enhance anastomotic safety in rectal surgery.

To compare the safety and feasibility of robot-assisted partial nephrectomy (RAPN) versus conventional laparoscopic surgery in patients with high-complexity renal tumours (RENAL score ≥ 10).

Previous studies have estimated the mean sojourn and dwell times within stages for commonly screened cancer types. However, little is known about the preclinical detection window of circulating tumor DNA (ctDNA) (ie, ctDNA positivity), which is important for understanding multicancer early detection.

The purpose of this study is to investigate the value of a radiomics model based on diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for preoperative prediction of telomerase reverse transcriptase (TERT) promoter mutation status in gliomas.

High-grade serous ovarian cancer (HGSOC) is characterized by a complex tumor microenvironment and poor prognosis, yet the roles of specific tumor-associated macrophages (TAMs) subpopulations in driving disease progression remain elusive.

Colorectal cancer (CRC) remains a significant global health concern. Improving the efficacy of immunotherapy, particularly for microsatellite-stable tumors, requires a better understanding of the unconventional T-cell populations that regulate intestinal immunity. γδ T cells are uniquely positioned at the epithelial barrier and function as rapid sentinels, recognizing stress signals independently of classical antigen presentation. In a healthy colon, γδ intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) form separate compartments influenced by tissue-specific butyrophilin-like (BTNL) interactions, microbiota-derived signals, and cytokine environments. These signals imprint divergent effector programs, ranging from IFN-γ-producing, cytotoxic responses to IL-17-driven tissue repair and inflammation. In CRC, however, these subsets exhibit remarkable plasticity. In mouse models, for example, Vγ1+ and Vγ7+ IELs mediate potent antitumor immunity, whereas Vγ4+ and Vγ6+ LPLs can acquire IL-17-dependent pro-tumor functions. In contrast, human data depict a different balance. Across multiple cohorts, tumor-infiltrating γδ T cells, predominantly the Vδ1+ and Vδ2+ subsets, exhibit robust cytotoxic and IFN-γ-associated phenotypes. Meanwhile, the existence of bona fide IL-17-producing γδ T cells remains highly controversial. Higher γδ T-cell abundance correlates with better outcomes, even in tumors with defective HLA class I expression, where γδ T cells can mediate the therapeutic effects of PD-1 blockade. Emerging findings reveal subset heterogeneity, context-dependent functional states, and a crucial role for NK-receptor-mediated recognition, particularly via NKG2D. Together, these insights position γδ T cells as pivotal yet understudied regulators of CRC progression and immunotherapy responsiveness. Understanding their subset-specific biology could lead to next-generation γδ-based therapies tailored to the unique immunogenic constraints of colorectal cancer.

Hematologic malignancies (HMs), which originate from hematopoietic or lymphoid tissues, pose a significant therapeutic challenge due to issues such as drug resistance, relapse, and treatment-related toxicity. The tumor microenvironment (TME), especially within the bone marrow niche, is now widely recognized as a critical determinant of disease progression and treatment response. A central mechanism within this specialized niche is the extensive metabolic reprogramming of key stromal and immune cells, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and bone marrow adipocytes (BMAds). This review systematically elaborates on the alterations in glucose, lipid, and amino acid metabolism within these cellular compartments of the HM-TME. We detail how metabolites such as lactate, fatty acids, and itaconate function not merely as metabolic byproducts but as active signaling molecules that drive critical processes like immune cell polarization, stromal remodeling, and intricate metabolic crosstalk. This comprehensive reprogramming collectively fosters a profoundly immunosuppressive milieu, promotes tumor cell survival and proliferation, and confers resistance to conventional and novel therapies. Furthermore, we explore emerging therapeutic strategies designed to target these metabolic vulnerabilities. These include inhibitors of specific metabolic pathways, modulators of metabolite-driven signaling, and innovative approaches such as nanomedicine and metabolically enhanced immunotherapy. Finally, we outline the current challenges in the field-such as intra-tumoral metabolic heterogeneity and the pressing need for targeted delivery systems-and discuss future perspectives involving advanced technologies like single-cell metabolomics and rational combination strategies. In summary, this synthesis aims to provide a comprehensive and rational foundation for developing novel immunometabolic interventions against HMs, highlighting the therapeutic potential of disrupting the metabolic dialogue within the TME.

Osteosarcoma remains a therapeutically challenging malignancy with durable responses limited by frequent treatment resistance. Although immune activity is detectable in many tumors, immunotherapy and combination strategies show limited clinical benefit, indicating immune dysfunction extends beyond tumor-intrinsic mechanisms. Growing evidence identifies immune exclusion as a key immunological barrier in osteosarcoma, characterized by spatial and functional segregation of immune cells from malignant areas despite their presence in the tumor microenvironment. Here, we use immune exclusion as a working term to describe contexts in which immune cells are present but have limited effective access to, or engagement with, malignant cells-distinct from immune desert (near-absence of infiltrates) and immune-cold states (weak effector activation despite some infiltration). In this mini-review, we focus on immune exclusion as a context-dependent immunological driver of treatment resistance in osteosarcoma. We integrate insights from single-cell sequencing, spatial profiling, and multi-omics studies to characterize the immunological features of immune exclusion, highlight bone-associated structural and regulatory factors, and explore how exclusion creates selective pressure leading to therapeutic failure. Emerging data indicate that immune exclusion represents a coordinated program involving tumor, stromal, and immune elements, resulting in impaired immune-tumor interaction and ineffective clearance. We discuss the translational implications, stressing immune-context modulation as essential for re-sensitization and noting that many current single-cell and spatial datasets remain limited in sample size, sampling sites, and treatment background. Framing resistance through immune exclusion offers an immune-centric framework for understanding and overcoming treatment resistance in osteosarcoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy characterized by marked cellular and spatial diversity within the tumor microenvironment (TME). The transforming growth factor-β (TGF-β) signaling pathway plays a dual role in the initiation and progression of HCC. However, the spatial distribution characteristics and key regulatory mechanisms of TGF-β signaling within HCC tissues remain inadequately elucidated.

Locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with poor prognosis and limited treatment options. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach. While previous meta-analyses have shown the efficacy and safety of ADCs in UC, the rapid development of new ADC agents and combination therapies necessitates an updated and comprehensive evidence synthesis.

Overcoming resistance to immune checkpoint inhibitors (ICIs) remains a critical challenge in the treatment for hepatocellular carcinoma (HCC).

Glioma-associated microglia/macrophages (GAMs) have traditionally been described as immunosuppressive. However, within their highly heterogeneous repertoire, pro-phagocytic and cytotoxic subsets with anti-tumoral properties exist. Although macrophages (MACs) can exhibit tumor-suppressive functions, their anti-glioma properties largely remain elusive. To identify anti-glioma myeloid cell effectors, we performed directionally concatenated ligand-receptor (L-R) interactome analyses from dendritic cells (DCs) and microglia (MG) to lymphoid (CD4+T, Tregs, CD8+T, NK, and NKT) cells identified by our recent single-cell transcriptomics interrogation of tumor-associated CD45+ leukocytes from tumor brains of eighteen isocitrate dehydrogenase (IDH)-stratified glioma patients. Within DC-specific and MG-specific interactomes, we identified LGALS9, which encodes Galectin-9, as a key mediator of cell-cell interactions in IDH-wild type (IDH-wt) gliomas. Spectral cytometry, immunohistochemistry, and Western blotting analyses confirmed the abundant expression of Galectin-9 in glioma-associated MG, but not in tumor cells. Furthermore, differential gene enrichment analyses revealed transcripts associated with cellular adhesion (coronin 1A, integrin) and phagocytosis (FcγR, phospholipase D, Rab family proteins, etc.) pathways that were significantly upregulated in Galectin-9+ compared to Galectin-9- MG and MACs. Using an ex-vivo primary human microglia (pMG) and patient-derived glioma stem cells (GSCs) co-culture system, we evaluated the functional role of Galectin-9. Confocal imaging analyses of co-cultured pMG with GSCs revealed that siRNA-mediated knockdown or antibody-based neutralization of Galectin-9 significantly impaired pMG-GSC adhesion. In addition to reduced adhesion, phagocytosis of GSCs was dramatically attenuated across all Galectin-9 silenced or neutralized pMG. Altogether, our study underscores the unappreciated non-canonical role of Galectin-9 in MG as a regulator of glioma cell adhesion and phagocytosis that can be harnessed for glioblastoma immunotherapy.

Head and neck squamous cell carcinoma (HNSCC) remains a highly aggressive malignancy with poor prognosis driven by metastasis and therapeutic resistance. Through comparative proteomic profiling of tumor specimens from patients with long‑ and short‑term survival, the present study identified leucine zipper protein 1 (LUZP1) as one of the most upregulated proteins in tumors from short‑term survivors. Functional assays revealed that LUZP1 knockdown impaired migration, invasion, invadopodia formation and epithelial‑mesenchymal transition, while enhancing sensitivity to docetaxel and cisplatin. Analysis of paired primary and metastatic tumors further confirmed elevated LUZP1 expression in metastatic sites. Mechanistically, NF‑κB inhibition markedly reduced LUZP1 expression, whereas stimulation with IL‑1β or TNF‑α induced its upregulation and rescued the migration defect caused by LUZP1 depletion, implicating NF‑κB as a key upstream regulator. Immunohistochemical analysis of clinical samples demonstrated that high LUZP1 expression was associated with shorter overall and progression‑free survival. Collectively, these findings identify LUZP1 as a novel NF‑κB‑regulated effector that promotes metastasis and chemoresistance and highlight its potential as a prognostic biomarker and therapeutic target in HNSCC.

Ribosomal RNA processing 9 (RRP9) encodes a WD‑repeat domain‑containing protein, which is a potential carcinogenic biomarker for various tumors. As a key structural component of small nucleolar ribonucleoproteins, RRP9 serves a key role in ribosome biogenesis by facilitating 18S rRNA processing. Despite its association with the pathogenesis of various malignancies, its function and molecular mechanisms in hepatocellular carcinoma (HCC) remain unknown. The present study aimed to examine the biological role of RRP9 in HCC progression and the underlying regulatory mechanisms. Immunohistochemical and western blot analyses revealed a significant downregulation of RRP9 expression in patients with HCC compared with matched adjacent non‑tumorous tissues. To investigate RRP9 biological functions in HCC, stable RRP9‑knockdown and ‑overexpressing isogenic HCC cell line models were established using lentiviral transduction and puromycin selection. Functional assays, including Cell Counting Kit‑8 viability, colony formation, wound healing migration and Transwell invasion experiments, consistently demonstrated that RRP9 significantly suppressed HCC cell viability, proliferation, invasion and migration. Transcriptome sequencing and western blot analyses indicated that RRP9 inhibited the PI3K/AKT/mTOR pathway. Furthermore, functional rescue assays using the PI3K activator 740 Y‑P and the inhibitor PI3K/AKT/mTOR‑IN‑2 verified that RRP9 exerts its tumor‑suppressive role via this pathway. Protein‑protein interaction analysis revealed an association between RRP9 and cyclin A2 (CCNA2). Western blotting confirmed that RRP9 downregulated CCNA2 expression. Additionally, subcutaneous tumorigenesis in mice showed that RRP9 inhibits liver cancer progression via the PI3K/AKT/mTOR signaling pathway.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the flow cytometric plots shown in Fig. 3 on p. 372, the C/U2OS and 48 h/U2OS, C/143B and 48 h/143B, and C/MG63 and 72 h/143B data panels, respectively, were strikingly similar, suggesting that this figure has been assembled incorrectly, and that these data were derived from a smaller number of original sources. The authors have been contacted by the Editorial Office to offer an explanation for the apparent duplication of these data panels within this figure, and we are waiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding 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 31: 370‑375, 2014; DOI: 10.3892/or.2013.2862].

Cancer‑associated fibroblasts (CAFs) play critical roles in the tumor microenvironment (TME); however, their characteristics under hypoxic conditions remain incompletely understood. The aim of the present study was to investigate the properties of hypoxic CAFs and identify their regulatory factors in colorectal cancer (CRC). CAFs cultured under normoxic and hypoxic conditions were analyzed using proliferation assays, co‑culture experiments, shotgun proteomics and single‑cell RNA sequencing. Clinical specimens were evaluated immunohistochemically using the desmoplastic reaction (DR) classification. In addition, the generalizability of the findings was validated by correlation analyses using The Cancer Genome Atlas database. Hypoxic CAFs showed enhanced proliferative capacity, and their conditioned medium promoted migration and chemoresistance in CRC cells. Shotgun proteomics revealed a significant increase in vitamin D‑binding protein in the conditioned media of hypoxic CAFs, while single‑cell RNA sequencing showed enrichment of genes related to bone metabolism and the phosphoinositide 3‑kinase‑AKT signaling pathway. Treatment of normal fibroblasts (NFs) with parathyroid hormone‑related protein (PTHrP) induced CAF‑like phenotypes, whereas treatment of CAFs with vitamin D led to morphological changes toward a NF‑like appearance. In clinical samples, the immature DR subtype, associated with poor prognosis, exhibited increased expression of the hypoxia marker hypoxia‑inducible factor‑1α, periostin and PTHrP, along with a significant association with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. Furthermore, a strong positive correlation was observed between the copy numbers of PTHrP and KRAS across multiple cancer types, including CRC. These findings suggest that the PTHrP‑vitamin D‑rat sarcoma oncogene (RAS) axis functions as an important regulatory mechanism in hypoxic CAFs. PTHrP and vitamin D may influence each other's activity, and this axis may contribute to tumor progression within the TME. Therefore, the PTHrP‑vitamin D‑RAS axis could serve as a potential therapeutic target.

The high mortality rates of prostate cancer correlate with patients who are diagnosed with bone metastasis. We have fabricated an innovative bioreactor with an injection port ideal for recapitulating the EMT (epithelial to mesenchymal transition) to MET (mesenchymal to epithelial transition) cascade of circulating prostate cancer cells. Further, the migration to bone by hypoxic cancer cells was evaluated under fluid flow. First, we demonstrated that hypoxia, an initiator of metastasis, activates αVβ3 integrins, leading to enhanced cell attachment and growth. We assessed the expression of αVβ3 and the MET biomarkers vimentin and E-cadherin to evaluate role of interstitial fluid flow on circulating prostate cancer cells. We observed upregulation of αV, β3, and E-cadherin expression in normoxic and hypoxic PC3 cells. Hypoxic PC3 cells expressed higher angiogenic markers such as VEGF (vascular endothelial growth factor), MMP-9 (matrix metalloproteinase protein-9), and FAK (focal adhesion kinase). We recapitulated the migration of clustered cells using hanging drop spheroids and observed different migratory pattern and that the crosstalk between PC3 cells and cancer-associated-fibroblasts alters the angiogenicity of cancer spheroids. Overall, this study showcases the ability of this bioreactor to mimic prostate cancer migration to bone under interstitial fluid flow. Understanding the migratory patterns of metastatic prostate cancer can help in predicting cancer progression and identifying appropriate therapies for patients with advanced-stage prostate cancer.