Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes

Daniel Abate-Daga, Ken Ichi Hanada, Jeremy L. Davis, James C. Yang, Steven A. Rosenberg, Richard A. Morgan

Research output: Contribution to journalArticle

Abstract

Despite significant progress in the development of adoptive cell-transfer therapies (ACTs) using gene-engineered T cells, little is known about the fate of cells following infusion. To address that, we performed a comparative analysis of gene expression between T-cell receptor–engineered lymphocytes persisting in the circulation 1 month after administration and the product that was infused. We observed that 156 genes related to immune function were differentially expressed, including underexpression of stimulators of lymphocyte function and overexpression of inhibitory genes in postinfusion cells. Of genes overexpressed postinfusion, the product of programmed cell death 1 (PDCD1), coinhibitory receptor PD-1, was expressed at a higher percentage in postinfusion lymphocytes than in the infusion product. This was associated with a higher sensitivity to inhibition of cytokine production by interaction with its ligand PD-L1. Coinhibitory receptor CD160 was also overexpressed in persisting cells, and its expression was associated with decreased reactivity, which surprisingly was found to be ligand-independent. These results contribute to a deeper understanding of the properties of transgenic lymphocytes used to treat human malignancies and may provide a rationale for the development of combination therapies as a method to improve ACT. This trial was registered at www.clinicaltrials.gov as #NCT00509288, #NCT00923195, and #NCT01273181.

Original languageEnglish (US)
Pages (from-to)1399-1410
Number of pages12
JournalBlood
Volume122
Issue number8
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes'. Together they form a unique fingerprint.

  • Cite this

    Abate-Daga, D., Hanada, K. I., Davis, J. L., Yang, J. C., Rosenberg, S. A., & Morgan, R. A. (2013). Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes. Blood, 122(8), 1399-1410. https://doi.org/10.1182/blood-2013-04-495531