Small cell lung cancer (SCLC) is an aggressive malignancy that responds poorly to immune checkpoint inhibitor (ICI) therapy, due to its immunosuppressive tumor microenvironment. Here, we analyse preclinical mouse tumor models and patient-derived SCLC samples and identify Exportin 1 (XPO1) as a regulator of immune suppression in SCLC. Mechanistically, XPO1 drives the nuclear export of TRIM21, enabling TRIM21-dependent proteasomal degradation of IRF3 and repressing the immunostimulatory cytokine TNFSF15. Loss of TNFSF15 promotes TREM2⁺ macrophage polarization, which subsequently attenuates macrophage-dependent IFN-γ-STAT1 signaling and MHC class I expression in tumor cells. Pharmacological or genetic XPO1 blockade restores TNFSF15, constrains TREM2⁺ macrophage differentiation, reactivates antigen presentation, and enhances anti-PD-1 efficacy in preclinical mouse models. Thus, our findings link XPO1-dependent nuclear export to TREM2+ macrophage polarization and support evaluation of XPO1 inhibition in combination with ICIs in SCLC.

Paragangliomas are rare neuroendocrine tumors occasionally found in the mediastinum. A characteristic CT presentation suffices to raise suspicions. Biopsy specimens are usually avoided, and diagnosis is generally based on a combination of biological, clinical and iconographic evidence.

We report on the case of an 84-year old female patient without adrenergic signs, who presented with an isolated mid-mediastinal lesion, which was found on FDG-TEP to be hypermetabolic. Its appearance was suggestive of a neuroendocrine tumor or a clear cell renal tumor, leading to investigation by EBUS-TBNA. The cytology aspirations subsequently performed were complicated by moderate bleeding, which was controlled by local instillations of adrenalized serum. An anatomopathological diagnosis of paraganglioma ensued, and was confirmed by further endocrinologic investigations.

Notwithstanding its technical feasibility, assessment of mediastinal paragangliomas by EBUS-TBNA may present an increased risk of moderate to severe bleeding. Appropriate safety measures should be considered, as well as diagnosis by non-invasive methods alone.

A man in his 70s was referred for urological evaluation because of a progressive increase in serum prostate-specific antigen levels. The patient had no significant lower urinary tract symptoms and no previous history of prostate cancer. Transabdominal ultrasound revealed a solid hypoechoic nodular lesion adjacent to the prostate in the right posterolateral periprostatic region, with inconclusive features and an indeterminate differential diagnosis. Multiparametric prostate MRI demonstrated a well-defined periprostatic nodule showing signal intensity, diffusion characteristics and contrast-enhancement patterns identical to those of the prostatic transitional zone. Based on imaging findings, heterotopic prostatic tissue was suspected. A targeted biopsy of the lesion was performed to exclude malignancy. Histopathological examination revealed benign prostatic glands with stromal components consistent with normal prostatic tissue, confirming the diagnosis of heterotopic prostatic tissue. The patient was managed conservatively, with reassurance and clinical follow-up, avoiding unnecessary aggressive treatment.

Systemic light chain (AL) amyloidosis is a clonal plasma cell dyscrasia characterised by extracellular deposition of misfolded amyloid fibrils composed of immunoglobulin light chains. These amyloid fibrils disrupt tissue architecture, ultimately leading to organ dysfunction. Clinical symptoms vary among cases, depending on the organs involved. The heart and kidney are the most commonly affected vital organs, whereas jejunal involvement is rare.We report a case of jejunal perforation associated with systemic AL amyloidosis during treatment of recurrent uterine cancer. The deposition of amyloid fibrils has also been identified in uterine cancer tissue specimens. Tracing back to her history, postprandial abdominal distension developed 3 years before jejunal perforation. This case highlights both the chronic and acute gastrointestinal manifestations of AL amyloidosis; however, diagnosis and treatment remain challenging in patients with such complex comorbidities.

Acute leukemia is a hematologic malignancy that affects people of all ages. Immunotherapies, including T-cell engagers, antibody-drug conjugates, and chimeric antigen receptor T-cell therapies have contributed to a paradigm shift in the treatment of patients with acute leukemia. Combined with advancements in allogeneic hematopoietic stem cell transplant and targeted therapy development, patients with acute leukemia have additional effective treatment options, providing the possibility of long-term remission. However, these advances have resulted in a complex and dynamic treatment landscape for clinicians to navigate. To guide the oncology community and provide a framework for patient care, the Society for Immunotherapy of Cancer convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of acute leukemia. Drawing from published data and clinical experience, the Expert Panel developed evidence-based and consensus-based recommendations relating to diagnostics; immunotherapies for the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, and blastic plasmacytoid dendritic cell neoplasm; toxicity and safety management; treatment sequencing; and patient education and quality of life.

Dual inhibition of indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) may alleviate suppression of antitumor immune responses by overcoming redundant immunosuppressive pathways. This study evaluated the combination of KHK2455, a novel and selective, long-lasting, and potent oral IDO1 inhibitor, with avelumab, a PD-L1 inhibitor, in adults with locally advanced or metastatic urothelial carcinoma.

This multicenter, open-label Phase 1 study evaluated the safety and tolerability of oral daily KHK2455 (30, 100, and 200 mg) plus intravenous avelumab (800 mg biweekly), the safety of KHK2455 200 mg monotherapy, KHK2455 and avelumab antitumor activity, avelumab antidrug antibodies, and combination therapy pharmacokinetics.

16 subjects were enrolled (n=4, 4, and 8 in the 30, 100 and 200 mg cohorts, respectively). No dose-dependency was observed for KHK2455-only related treatment-emergent adverse events (TEAEs). No TEAEs were considered related to KHK2455 or avelumab. Four subjects had fatal TEAEs considered not related to treatment.One subject in the KHK2455 30 mg cohort achieved a complete response (CR) and one in the KHK2455 200 mg cohort achieved a partial response (PR), both with avelumab.PD-L1 expression was evaluated in the 13 available baseline tumor biopsy samples. All biopsies expressed PD-L1 in at least one compartment; 31% (4/13) were positive on tumor cells and 69.2% (9/13) were positive on tumor-associated immune cells. Over half (53.8%, 7/13) expressed PD-L1 at high levels and within the disease control group consisting of CR (n=1), PR (n=1) and stable disease (n=5), 57.1% (4/7) were PD-L1 high. Baseline expression profiles showed significantly higher immune activation in the subject with CR compared with the subject with PR and those with progressive disease. The subject with CR had the highest baseline Tumor Inflammation Signature (TIS) score (9.06) compared with 4.8 in the subject with PR and lower TIS score values in subjects with progressive disease. Changes in gene expression were observed, including upregulation of CXCL12, CCND2, and MMRN2, and downregulation of HLA-DRB5, CRABP2, and VEGFA in responders versus progressive disease comparisons.

The favorable safety profile and preliminary efficacy results of KHK2455 in combination with avelumab, along with the translational biomarker findings, warrant further investigation.

Anastomotic leakage remains one of the most serious complications after low anterior resection for rectal cancer. The modified single-stapled technique (MST) eliminates the intersection between linear and circular staple lines and may reduce leakage compared with the conventional double-stapled technique (DST). This trial aims to determine whether MST reduces anastomotic leakage in patients undergoing laparoscopic or robotic low anterior resection.

This is a multicentre, parallel-group and superiority randomised controlled trial conducted in six tertiary hospitals in South Korea. A total of 450 patients undergoing laparoscopic or robotic low anterior resection for rectal cancer will be randomised in a 1:1 ratio to MST or DST. Randomisation will be stratified by sex and neoadjuvant treatment. The primary outcome is anastomotic leakage within 30 days after surgery, confirmed by clinical findings and routine postoperative abdominopelvic CT. Secondary outcomes include additional distal resection margin length, local recurrence, 3-year disease-free survival and overall survival. Analyses will follow the intention-to-treat principle.

The study was approved by the Institutional Review Board of Korea University Anam Hospital (2025AN0114). Results will be disseminated through peer-reviewed journals and scientific meetings.

NCT07376980.

Pharmacoepidemiologic studies using real-world data often lack clinical context, much of which is embedded in free-text electronic health records (EHRs). However, sharing EHR narratives is restricted by privacy requirements, and conventional deidentification approaches may reduce analytic utility and limit auditability.

To develop and evaluate a framework that (1) extracts structured cancer-related entities from Japanese EHR free text using BERT (Bidirectional Encoder Representations from Transformers)-based natural language processing (NLP) and (2) generates deidentified analytic text that preserves contextual information to support post-hoc auditing under privacy constraints.

We conducted a retrospective observational study using the DATuM IDEA database, which integrates unstructured EHR narratives with structured records (claims, prescriptions, and procedure/surgery records) from two hospitals in Japan from January 1, 2019, through June 30, 2025. Deterministic linkage was performed within ICI (Integrated Clinical Care Informatics, Inc.) prior to deidentification. The source text population comprised all linked progress notes from eligible oncology patients. Downstream recoverability analyses were conducted within a governance-constrained analyzable text cohort derived after deidentification and preprocessing. We quantified deidentification using masking rates and residual visible character density and evaluated downstream recoverability of TNM/stage-related mentions, internal logical consistency (M1 vs Stage IV), and proxy-based concordance using structured-data treatment proxies (ATC code L for systemic anticancer therapy and procedure-name keyword searches for cancer-directed interventions). A stratified manual audit of 400 deidentified narratives was conducted primarily to inspect for apparent residual direct identifiers, with retention of intended TNM and stage outputs reviewed as a secondary sanity check.

Among 51,876 patients with recorded diagnoses, 10,214 had neoplasms (ICD-10 C00-D48), and linked progress notes were available for 4,383 patients (82,863 records). The downstream analyzable text cohort (Layer C), used for downstream recoverability and proxy-based concordance analyses, comprised 3,689 patients and 38,841 documents. Of these, 1,339 patients (36.3%) and 11,914 documents (30.7%) had at least one recoverable TNM or stage mention (Layer D). Across all Layer C documents, marginal document-level recoverability was 24.2% for T, N, and M elements and 23.6% for stage. Conditional on Layer D, the corresponding recoverability rates were 0.788 for T, 0.787 for N, 0.788 for M, and 0.768 for stage. Median masking rates ranged from 9.9% to 15.0% across major cancer categories. M1 and Stage IV mention indicators showed an overall agreement of 94.7%, a positive percent agreement (PPA) of 54.8%, and a negative percent agreement (NPA) of approximately 99.0%. Proxy-based concordance analysis showed a positive predictive value (PPV) of 0.700 for Stage IV using the systemic therapy proxy and a PPV of 0.031 for early-stage classification using the procedure proxy. Manual audit demonstrated retention of intended TNM/stage-related outputs after normalization and identified no apparent residual direct identifiers in the audited deidentified narratives.

This framework enables the generation of deidentified Japanese EHR narratives that preserve contextual structure for auditing while supporting structured entity extraction, thereby addressing the trade-off between privacy protection and reproducibility in real-world data research.

Pyroptosis is a gasdermin-mediated form of inflammatory cell death that may alter tumour-immune interactions. Its canonical, non-canonical and granzyme-associated pathways, together with NINJ1-dependent terminal membrane rupture, are reviewed here. Whether these mechanisms promote antitumour immunity or sustained inflammation depends on biological context. Pediatric ovarian and adnexal neoplasms include germ-cell tumours (GCTs), sex cord-stromal tumours (SCSTs), and less-common epithelial or other lesions. Histology, age, pubertal status, hormonal secretion, stage, and treatment exposure vary substantially across patients. Direct studies of pyroptosis and immune remodelling in these paediatric histologies remain scarce; evidence from adult epithelial ovarian cancer, non-ovarian tumours, cell lines, and mice cannot be treated as proof of a paediatric mechanism. This review retains a histology-specific framework to examine molecular pathways, the paediatric ovarian tumour immune microenvironment (TIME), candidate therapeutic approaches, and biomarkers. Established molecular or clinical observations are separated from cross-tumour extrapolations and untested hypotheses. Particular attention is paid to developmental immunity, endocrine context, on-target and off-target inflammation, and evidence required before clinical translation.

Most Triple Negative Breast Cancers (TNBCs) are p53 mutant high-grade invasive ductal carcinomas with a basal-like transcriptional programme. A large proportion of TNBCs also have mutation signatures indicating defective homologous recombination (HR) DNA repair. While HR deficiency is mutagenic and oncogenic, it can also compromise cell fitness. Here, we show that BLBCs harbouring the recurrent 9p21.3-9p24 amplicon, and particularly those that are HR-defective, overexpress PUM3 (Pumilio RNA binding family member 3). PUM3 inhibition is also synthetic lethal in tumour cells that overexpress PUM3 including those that have BRCA1/BRCA2 defects. Mechanistically, PUM3 suppresses transcription-mediated replicative stress and R-loop accumulation, thereby preventing DNA damage that would normally require RAD51-mediated repair. Transcription/replication collisions are commonly resolved by topoisomerase TOP1; without PUM3, TOP1 DNA chromatin localisation is impaired, revealing one mechanism by which PUM3 limits replication stress. PUM3 is therefore required for the continued fitness of a BLBC subset, allowing tolerance of HR deficiency's deleterious effects.