Metastatic disease is the prime cause of death from many malignancies. Due to the multiple different lesions and the increased aggressiveness of the cancer cells, metastatic disease is often difficult to treat. Here, the introduction of immune checkpoint blockers (ICBs) has greatly helped to improve patients' prognosis by harnessing antitumor immunity, particularly anticancer T cells in multiple human cancers. Despite the success of ICBs in, for example, metastatic melanoma 2 major challenges remain in the field: therapy-limiting toxicities induced by systemic ICB administration and lack of a life-prolonging response in a substantial number of patients. Therefore, highly potent local immunotherapeutic approaches might offer a solution and enhance treatment of metastatic disease. Here, we describe antibody-functionalized paramagnetic microbeads as a means to fill this void. These microbeads are readily engulfed by the vast majority of human cancer cell line cells studied inducing direct cytotoxicity (first hit). Focusing on malignant melanoma, we further observed that loading the microbeads with a conventional anti-CD28 monoclonal antibody (bead-bound conventional anti-CD28 monoclonal antibody, BBC-28) not only efficiently induced proliferation and cytokine release by human T cells expressing CD28, but also enhanced killing of melanoma cells by melanoma-reactive T cells (second hit). Thus, we provide proof-of-concept data that BBC-28, after local application into, for example, skin metastases, may also induce a combination of direct toxicity and enhanced anticancer immunity, leading to efficient treatment of metastatic disease.

A 77-year-old man with papillary thyroid carcinoma had received radioactive iodine therapy for metastatic disease 8 years earlier and subsequently achieved remission. He represented with rising serum thyroglobulin levels, and biopsy of newly detected cutaneous lesions confirmed metastatic disease. Posttherapy 131I SPECT/CT after 200 mCi demonstrated multiple radioiodine-avid cutaneous metastases involving the scalp, left auricular region, anterior chest wall, and dorsal region. This case highlights an exceptionally uncommon presentation of extensive, multifocal, radioiodine-avid cutaneous metastases detected on post-therapy 131I SPECT/CT after a long disease-free interval.

Merkel cell carcinoma (MCC)is a rare but aggressive cutaneous malignancy with increasing incidence and poor prognosis. Host immune status is a key determinant of MCCmerkel cell carcinoma development and outcome. While the AEIOU criteria are widely used to facilitate clinical recognition, their value for prognostic assessment remains unclear. To evaluate the association between individual AEIOU presentation features and disease progression in patients with merkel cell carcinoma, with particular emphasis on immunosuppression. We performed a retrospective single-centre cohort study including 400 patients diagnosed with merkel cell carcinoma. Disease progression, defined as local recurrence, nodal involvement or distant metastasis, served as the primary endpoint. AEIOU criteria were assessed at diagnosis and analysed using logistic regression. Complete follow-up data were available for 241 patients, of whom 81 (33.6%) experienced disease progression. Patients with progression were significantly older and more frequently male. Among the AEIOU components, immunosuppression was the only criterion significantly associated with disease progression, conferring an increased risk compared with immunocompetent patients (p<0.001). Other AEIOU features showed no consistent prognostic association. Complete follow-up data were available for 241 patients, of whom 81 (33.6%) experienced disease progression. Patients with progression were significantly older and more frequently male. Among the AEIOU components, immunosuppression was the only criterion significantly associated with disease progression, conferring an increased risk compared with immunocompetent patients (p<0.001). Other AEIOU features showed no consistent prognostic association.

Plasma proteins are increasingly recognized as key regulators of extracellular vesicle (EV) behaviour in circulation. However, von Willebrand factor (vWF)-the largest multimeric glycoprotein in blood and the only blood protein activated by shear-has received little attention in this context. Under elevated shear stress, vWF transitions from a compact globular form to an extended adhesive conformation. Although elevated plasma vWF levels are associated with hypercoagulation in conditions such as malaria, COVID-19, and cancer, its interactions with EVs or cells under physiological flow have not been systematically investigated. Here, we show that shear-activated vWF functions as a size-selective molecular filter that preferentially captures objects smaller than ∼4 µm, including platelets and tumour-derived EVs, while excluding larger cells. Although intact tumour cells do not directly bind vWF under physiological flow, the coordinated binding of EVs and platelets to extended vWF promotes platelet aggregation, which subsequently traps circulating tumour cells and fosters metastatic dissemination. Our findings reveal a previously unrecognized role of vWF as a shear-dependent EV-binding protein that brings EVs and platelets together to enhance coagulation and metastasis. These EV-vWF-platelet aggregates may represent promising biomarkers or therapeutic targets for the prevention of hypercoagulation in cancer and other thrombo-inflammatory diseases.

Primary angiosarcoma of the breast is an uncommon and aggressive vascular malignancy that typically affects young women and poses diagnostic and therapeutic challenges. We report the case of a 26-year-old nulliparous woman who presented with progressive left breast swelling over approximately 18 months. Clinical examination revealed diffuse tender swelling without skin discoloration, nipple changes, or palpable lymphadenopathy. Ultrasonography demonstrated a complex cystic mass with thick septations and increased vascularity, while mammography showed global asymmetry of the left breast without suspicious calcifications. Breast MRI revealed a large 8.4 cm heterogeneously enhancing mass in the upper outer quadrant with possible focal skin involvement, but no chest wall invasion or nodal disease. Initial staging with 18F-FDG PET/CT showed no distant metastases. The patient underwent left nipple-sparing mastectomy, and histopathological examination confirmed intermediate-grade primary mammary angiosarcoma, FNCLCC grade 2. Subsequent re-excision achieved clear surgical margins. She received adjuvant ifosfamide-epirubicin chemotherapy and radiotherapy. Initial follow-up imaging showed no residual or recurrent disease. However, 14 months after completion of treatment, follow-up 18F-FDG PET/CT demonstrated new FDG-avid lytic lesions in the sacral and iliac bones, and Breast MRI revealed a small enhancing sternal lesion, consistent with delayed osseous metastatic disease. The patient was treated with palliative radiotherapy and systemic therapy. This case highlights the diagnostic complexity of primary breast angiosarcoma, its potential for delayed hematogenous osseous spread, and the value of multimodality imaging in diagnosis, staging, treatment planning, and surveillance.

Numerous studies have reported the biological activities of tilapia skin oligopeptides, which exhibit diverse physiological effects. However, research on the relationship between peptide structural characteristics and their activities remains relatively scarce. In this study, we combined computational simulations with biological experiments to investigate the anti-metastatic mechanism of the tilapia skin oligopeptide LSGYG. Computational analyses supported recurrent Zn-neighboring and pocket-associated recognition modes of LSGYG in the catalytic region of matrix metalloproteinase-2 (MMP-2) and identified a dynamically retained pocket-stabilized state with near-Zn anchoring features. Pulling-guided umbrella-window screening further provided qualitative support for a local metastable region near the Zn-adjacent catalytic microenvironment. Subsequent in vitro evaluations demonstrated that LSGYG significantly suppressed migration and invasion in phorbol-12-myristate-13-acetate (PMA)-induced HT1080 cells and reduced metastasis-related molecular signaling in both HT1080 and 143B cells. Mechanistically, LSGYG substantially disrupted extracellular matrix (ECM) remodeling and epithelial-mesenchymal transition (EMT)-like changes by downregulating MMP-2, MMP-9, N-cadherin, Vimentin, and the upstream regulator hypoxia-inducible factor-1α (HIF-1α), while restoring E-cadherin expression. These phenotypic reversals were associated with suppression of reactive oxygen species (ROS), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and nuclear factor kappa-B (NF-κB) signaling pathways. These findings support LSGYG as a tilapia-derived bioactive peptide candidate for anti-metastatic functional-food or nutraceutical development.