ArticleThe Journal of clinical investigation2025
Double-positive T cells form heterotypic clusters with circulating tumor cells to foster cancer metastasis.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Review
- NNMT-associated metabolic-thromboinflammatory-immune co-activation in heterogeneous CTC clusters: a hypothesis-generating computational framework".BMC cancer · 2026Article
- Interactions Between Circulating Tumor Cells and the Immune System in Colorectal Cancer: Friends or Foes?Cancers · 2026Review
- Identification of epithelial, mesenchymal, and platelet-associated circulating tumour cells with translational implications in oral squamous cell carcinoma.Scientific reports · 2026Article
- CTC cluster in breast cancer: synergetic metastasis promotion mechanism and transformation path from platelet cloaking to leukocyte escort.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.NPJ breast cancer · 2026Review
- Study on the Potential Molecular Mechanisms of Sodium Dehydroacetate (Na-DHA) Interfering With Bone Metabolism and Inducing Osteoporosis Based on Network Toxicology, Molecular Docking, and In Vitro Experimental Validation.Food science & nutrition · 2026Article
- Article
- Immunosuppressive cells as barriers to cancer therapy: mechanisms and emerging solutions.Frontiers in immunology · 2026Review
- Caught in the Act: Tumor-Immune Interactions in Circulation of Patients with Immune Marker Positive Circulating Tumor Cells.Cancers · 2025Article
- Advancing Cancer Biology: Highlights from the 2025 FASEB SRC on Cellular Plasticity in Cancer.Cancer heterogeneity and plasticity · 2025Article
Corrections and comments
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19 authors.
Funding
Abstract
The immune ecosystem is central to maintaining effective defensive responses. However, it remains largely understudied how immune cells in the peripheral blood interact with circulating tumor cells (CTCs) in metastasis. Here, blood analysis of patients with advanced breast cancer revealed that over 75% of CTC-positive blood specimens contained heterotypic CTC clusters with CD45+ white blood cells (WBCs), which correlates with breast cancer subtypes, racial groups, and decreased survival. CTC-WBC clusters included overrepresented T cells and underrepresented neutrophils. Specifically, a rare subset of CD4 and CD8 double-positive T (DPT) cells was 140-fold enriched in CTC clusters versus their frequency in WBCs. DPT cells shared properties with CD4+ and CD8+ T cells but exhibited unique features of T cell exhaustion and immune suppression. Mechanistically, the integrin heterodimer α4β1, also named very late antigen 4 (VLA-4), in DPT cells and its ligand, VCAM1, in tumor cells are essential mediators of DPT-CTC clusters. Neoadjuvant administration of anti-VLA-4 neutralizing antibodies markedly blocked CTC-DPT clusters, inhibited metastasis, and extended mouse survival. These findings highlight a pivotal role of rare DPT cells in fostering cancer dissemination through CTC clustering. It lays a foundation for developing innovative biomarker-guided therapeutic strategies to prevent and target cancer metastasis.
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