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2026, 38(5): 555-558.
doi: 10.21147/j.issn.1000-9604.2026.05.01
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Abstract:
2026, 38(5): 572-575.
doi: 10.21147/j.issn.1000-9604.2026.05.05
Abstract:
2026, 38(5): 576-589.
doi: 10.21147/j.issn.1000-9604.2026.05.06
Abstract:
ObjectiveLong-term outcomes in T-lymphoblastic lymphoma (T-LBL) remain incompletely characterized by conventional survival estimates. We aimed to estimate statistical cure and describe landmark-updated survivorship in a multicenter T-LBL cohort defined by tissue diagnosis of a T-lineage lymphoblastic neoplasm with a mass-dominant presentation. MethodsWe analyzed 220 patients diagnosed during 2003−2026 at four Chinese centers. Four relative-survival cure models using age-, sex-, and calendar year-matched Chinese population life tables were fitted, with cure timing summarized by a 5% uncured-survival threshold. Landmark analyses at 6, 12, and 24 months assessed subsequent overall survival (OS), progression/relapse status, and exploratory landmark-updated scores. Internal assessment used 500 bootstrap resamples; a population-based Surveillance, Epidemiology, and End Results (SEER) cohort corroborated long-term survivorship patterns. ResultsMedian follow-up was 60.9 months and 5-year OS was 60.7%. Across models, cure fractions ranged from 57.8% to 59.3% and 5% uncured-survival threshold times ranged from 4.82 to 7.27 years. The principal non-mixture log-logistic model estimated a 57.8% cure fraction and a 7.27-year threshold (bootstrap 95% confidence interval, 4.83−11.65). This threshold exceeded the last observed death (6.24 years) and median follow-up (60.9 months) and therefore represented parametric extrapolation. Landmark cohorts included 193, 161, and 121 patients, with 60, 47, and 26 subsequent deaths. After age and diagnosis-year adjustment, pre-landmark progression/relapse remained associated with subsequent mortality (hazard ratios, 3.32, 3.07, and 3.21). Conditional optimism-corrected concordance indices (C-indices) for the exploratory equal-weight score were 0.696, 0.695, and 0.654; ridge weighting showed no consistent advantage. The 6-month split-sample test-set C-index was 0.498, indicating uncertainty in discrimination. SEER qualitatively corroborated a similar long-term survival pattern. ConclusionsThe findings support a long-term survival pattern consistent with population-level statistical cure and the prognostic relevance of updated disease status. Exact cure-time estimates remain model dependent, and the exploratory landmark-updated scores require independent validation before clinical use.
2026, 38(5): 590-605.
doi: 10.21147/j.issn.1000-9604.2026.05.07
Abstract:
ObjectiveThe immunological consequences of sparing uninvolved axillary lymph nodes (LNs) in breast cancer remain unclear. We asked whether a transcriptomically defined progenitor-exhausted-like (Tpex-like) CD8+ T-cell compartment is confined to the sentinel node or distributed across the axillary basin. MethodsWe integrated single-cell transcriptomics, paired T-cell receptor (TCR) profiling, and complementary flow cytometry across 15 patients (163,600 cells). We characterized Tpex-like CD8+ T cell populations and assessed their distribution, clonal expansion, and TCR clonotype sharing across sentinel and downstream non-sentinel uninvolved lymph nodes. Complementary flow cytometry was performed to evaluate progenitor-associated T-cell phenotypes at the protein level. ResultsUninvolved LNs were enriched for a C00 Tpex-like cluster characterized by relative enrichment of progenitor-associated TCF7 together with partial exhaustion-lineage features, including TOX expression and TCF7-TOX co-detection, but sparse PDCD1 transcript detection. C00 clonotypes were shared with tumor-infiltrating lymphocytes, whereas metastatic involvement was associated with reduced representation of this compartment. C00 abundance and clonotype-associated properties showed no clear positional differences across sentinel and downstream non-sentinel uninvolved nodes. Independently, flow cytometry detected TCF7/PD-1/TOX progenitor-like phenotypes in downstream non-sentinel uninvolved nodes from five patients; these protein-defined populations were not assumed to be identical to C00. ConclusionsAnatomically distinct uninvolved axillary LNs contain a broadly distributed transcriptomically defined C00 Tpex-like compartment, with complementary protein-level evidence for TCF7+PD-1+TOX+ progenitor-like phenotypes. These findings provide a biological framework for considering the immune architecture preserved by axillary de-escalation.
2026, 38(5): 606-623.
doi: 10.21147/j.issn.1000-9604.2026.05.08
Abstract:
ObjectiveBrain metastasis (BrM) is a common complication of advanced lung cancer with extremely poor prognosis. This study aimed to establish a molecular classification system for stratifying non-small cell lung cancer (NSCLC)-BrM patients and predicting survival, and to identify key BrM-related molecules and elucidate their mechanisms as potential therapeutic targets. MethodsWe integrated single-cell and bulk transcriptomic data to construct molecular subtyping models for predicting lung cancer prognosis and immune microenvironment, and to screen key molecules driving BrM. Based on H1299 and PC9-BrM cells, in vitro experiments demonstrated the regulatory role and mechanism of targeting protein for Xklp2 (TPX2) in lung cancer BrM. ResultsWe identified 20 BrM-associated genes. Consensus clustering based on these genes stratified patients into two subtypes, with patients in Subtype 2 showing significantly worse overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). Mechanistic analyses revealed marked activation of proliferation-related pathways in Subtype 2. TPX2 was identified as a critical mediator, with significantly elevated expression in BrM lesions compared with primary lung cancer lesions, and TPX2 overexpression correlated with poorer prognosis. Functional assays in H1299 and PC9-BrM cells demonstrated that TPX2 knockdown markedly impaired proliferation, clonogenicity, migration, and invasion. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and Western blotting validation further indicated that TPX2 likely promotes NSCLC-BrM by activating c-MYC and the epithelial-mesenchymal transition (EMT) process. ConclusionsOur study established a molecular classification system that effectively stratifies NSCLC-BrM patients and predicts survival. Moreover, TPX2 promotes NSCLC-BrM through c-MYC/EMT regulation, offering new insights for targeted therapeutic strategies.
2026, 38(5): 624-644.
doi: 10.21147/j.issn.1000-9604.2026.05.09
Abstract:
ObjectiveThis study aimed to systematically investigate the heterogeneity and correlations between variables within the tumor microenvironment (TME) of primary and metastatic pancreatic neuroendocrine tumors (PanNETs) using digital spatial profiling. MethodsData from 63 PanNET patients were analyzed, and two distinct sample cohorts were selected for in-depth evaluation. Based on the composition and density of infiltrating immune cells and stromal characteristics, three distinct TME subtypes were identified: T1 (deficient, D), T2 (immune-enriched, IE), and T3 (immune- and fibroblast-enriched, IE/F). ResultsThe three TME subtypes exhibited distinct clinical prognostic significance, with subtype T3 (IE/F) being associated with the lowest overall survival rates, particularly in metastatic disease (MT3). Molecular characterization revealed substantial variations in gene and protein expression profiles among the subtypes. We further developed an eight-gene prognostic model specifically for identifying MT3 (IE/F), which demonstrated enhanced accuracy for predicting patient survival compared to conventional pathological grading systems. ConclusionsThese findings provide critical insights into the complexities of TME and offer a potential framework for personalized treatment strategies for PanNET patients.
2026, 38(5): 645-660.
doi: 10.21147/j.issn.1000-9604.2026.05.10
Abstract:
ObjectiveResidual cancer after irreversible electroporation (IRE) is usually discussed in relation to treatment margins and field coverage. We asked whether surviving prostate cancer cells also pass through a time-limited damage-recovery sequence that can be targeted with olaparib. MethodsWe analyzed complementary transcriptomic datasets from distinct systems: single-cell RNA sequencing of RM1-luc tumors in C57BL/6 mice and bulk RNA sequencing of 22Rv1 cells after IRE. DNA damage, cell viability, colony formation, apoptosis and Ser139-phosphorylated histone H2AX (γH2AX) were examined in 22Rv1 and PC3 cells. The effect of adding olaparib after IRE was then tested in BALB/c nude mice bearing 22Rv1-luc xenografts. ResultsIRE was accompanied by transcriptional changes in DNA damage response, checkpoint and repair-associated pathways. In xenografts and exploratory, independent and non-paired human tissue specimens (n=4 per group), IRE increased γH2AX staining, although IRE alone provided only limited short-term tumor control. In vitro, IRE reduced cell viability, increased the percentage of DNA in the tail (Tail DNA %) in alkaline comet assays and impaired colony formation. The DNA damage signal later declined, consistent with partial reversibility. Low-dose olaparib prolonged the persistence of IRE-induced DNA damage, maintained stronger γH2AX signals and increased apoptosis. In vivo, IRE plus olaparib resulted in lower tumor volume, tumor weight and bioluminescent signal than either treatment alone, with no marked body-weight loss during the short observation period. ConclusionsIRE induced a transient repair-associated vulnerability in prostate cancer models. Olaparib delayed the resolution of this damage and enhanced short-term antitumor activity following IRE, suggesting a repair-targeted sensitization strategy that merits further study.
2026, 38(5): 661-678.
doi: 10.21147/j.issn.1000-9604.2026.05.11
Abstract:
ObjectiveTherapeutic resistance remains a major challenge in bladder cancer treatment. The aim of this study was to develop and validate a bladder cancer patient-derived organoid (PDO)-based platform for treatment response prediction and individualized salvage therapy screening. Methods A total of 101 patients with bladder cancer were enrolled to establish 75 PDO lines. The optimal culture medium was determined by transcriptome analysis. Consistency validation was performed via histopathology, immunohistochemistry, whole-exome sequencing, and transcriptomic profiling. A three-step high-throughput screening pipeline for 288 approved agents was developed to identify salvage therapies for patients who were multidrug-resistant, which was validated in patient-derived xenograft (PDX) models. A suspension coculture system was constructed to evaluate HER2-targeted chimeric antigen receptor T (CAR-T) cell cytotoxicity and activation. Results FGF4 supplementation significantly enhanced the 3D growth and establishment efficiency of PDOs, yielding a biobank of 75 bladder cancer PDOs. These PDOs faithfully recapitulated the multidimensional features of parental tumors, and showed preliminary concordance with observed clinical treatment responses (cisplatin, gemcitabine, and epirubicin). To address drug resistance, the high-throughput drug screening pipeline maps individualized sensitivity profiles in four cases. In a patient who was multidrug-resistant, idarubicin was pinpointed as a potent candidate agent, with efficacy confirmed in PDX models. To extend the screening platform beyond chemotherapeutics and cover cellular immunotherapies, we verified that the coculture system enabled HER2 expression-dependent CAR-T cytotoxicity evaluation. Conclusions This integrated bladder cancer PDO platform provides a clinically relevant individualized tool for treatment response prediction and individualized salvage therapy selection, particularly for patients with multidrug-resistant disease. Its application may support tailored therapeutic decision-making across chemotherapy, targeted therapy, and cellular immunotherapy.
