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September 16, 2025Journal of Clinical InvestigationOpen Access

Double-positive T cells form heterotypic clusters with circulating tumor cells to foster cancer metastasis

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Authors

DSDavid ScholtenNorthwestern UniversityLELamiaa El-ShennawyNorthwestern UniversityYJYuzhi Jia

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Implication

Blood analysis shows double-positive T cells cluster with circulating tumor cells, indicating a role in metastasis. Neoadjuvant anti-VLA-4 antibodies inhibit these clusters and may enhance survival.

Key Points

  • Over 75% of CTC-positive blood samples contained clusters with double-positive T cells, indicating a fundamental role in metastasis.
  • A rare subset of double-positive T cells was found to be 140-fold enriched in CTC clusters, which correlates with certain breast cancer subtypes.
  • The integrin α4β1 in T cells and its ligand VCAM1 in tumor cells are crucial for the clustering of double-positive T cells and CTCs.
  • Neoadjuvant treatment with anti-VLA-4 neutralizing antibodies significantly reduced CTC-DPT clusters, highlighting a potential therapeutic target.

Cite This Study

Scholten et al. (2025) studied this question.

synapsesocial.com/papers/68d42336713b0b5dfea6b64bhttps://doi.org/10.1172/jci193521
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