Selection of CD8++PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells

Takashi Inozume, Ken Ichi Hanada, Qiong J. Wang, Mojgan Ahmadzadeh, John R. Wunderlich, Steven A. Rosenberg, James C. Yang

Research output: Contribution to journalArticle

Abstract

CD8+ tumor-infiltrating lymphocytes (TILs) in human melanomas express high levels of PD-1 and are functionally impaired. However, adoptive cell therapy using in vitro-expanded TIL can be a highly effective therapy for patients with advanced melanoma. This discrepancy led us to further analyze the CD8+PD-1+ TILs. We found that the percentage of PD-1-expressing CD8+ T cells was higher in the tumor digests that generate tumor-reactive TILs after in vitro culture in interleukin-2 (P=0.0007). Also sorted and expanded CD8+PD-1+ T cells in tumor digests showed much higher tumor-specific interferon-γ production compared with CD8+PD-1 T cells. These results suggested that tumor-specific CD8+ T cells in melanoma tumor digests are largely PD-1+, and this population can recover function after culturing in interleukin-2. PD-1 has been reported as an inhibitory receptor on T cells. We found that the in vitro functional suppression of cultured-TILs from native levels of PD-L1 expression on melanomas was minimal, and moreover expression level of PD-1 on CD8+ tumor-specific TILs decreased during the culture. As a consequence, the PD-1 receptor can be a useful biomarker for enriching tumor-specific T cells from fresh melanomas.

Original languageEnglish (US)
Pages (from-to)956-964
Number of pages9
JournalJournal of Immunotherapy
Volume33
Issue number9
DOIs
StatePublished - Nov 1 2010

Keywords

  • PD-1
  • PD-L1
  • TIL
  • melanoma
  • tumor digest
  • tumor immunity
  • tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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    Inozume, T., Hanada, K. I., Wang, Q. J., Ahmadzadeh, M., Wunderlich, J. R., Rosenberg, S. A., & Yang, J. C. (2010). Selection of CD8++PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. Journal of Immunotherapy, 33(9), 956-964. https://doi.org/10.1097/CJI.0b013e3181fad2b0