Isolation of tumour-reactive lymphocytes from peripheral blood via microfluidic immunomagnetic cell sorting

Zongjie Wang, Sharif Ahmed, Mahmoud Aziz Mahmoud Labib, Hansen Wang, Licun Wu, Fatemeh Bavaghar-Zaeimi, Nastaran Shokri, Soraly Blanco, Saraf Karim, Kasia Czarnecka-Kujawa, Edward H. Sargent, A. J.Robert McGray, Marc de Perrot, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The clinical use of tumour-infiltrating lymphocytes for the treatment of solid tumours is hindered by the need to obtain large and fresh tumour fractions, which is often not feasible in patients with unresectable tumours or recurrent metastases. Here we show that circulating tumour-reactive lymphocytes (cTRLs) can be isolated from peripheral blood at high yield and purity via microfluidic immunomagnetic cell sorting, allowing for comprehensive downstream analyses of these rare cells. We observed that CD103 is strongly expressed by the isolated cTRLs, and that in mice with subcutaneous tumours, tumour-infiltrating lymphocytes isolated from the tumours and rapidly expanded CD8+CD103+ cTRLs isolated from blood are comparably potent and respond similarly to immune checkpoint blockade. We also show that CD8+CD103+ cTRLs isolated from the peripheral blood of patients and co-cultured with tumour cells dissociated from their resected tumours resulted in the enrichment of interferon-γ-secreting cell populations with T-cell-receptor clonotypes substantially overlapping those of the patients’ tumour-infiltrating lymphocytes. Therapeutically potent cTRLs isolated from peripheral blood may advance the clinical development of adoptive cell therapies.

Original languageEnglish (US)
Pages (from-to)1188-1203
Number of pages16
JournalNature Biomedical Engineering
Issue number9
StatePublished - Sep 2023

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Computer Science Applications


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