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

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.

• Authors: Takashi Inozume, Ken-Ichi Hanada, Qiong J Wang, Mojgan Ahmadzadeh, John R Wunderlich, Steven A Rosenberg, James C Yang
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2010 Nov-Dec Vol. 33 Issue 9 Pg. 956-64 ISSN: 1537-4513 [Electronic] United States
• PMID: 20948441 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Antigens, Neoplasm
• Apoptosis Regulatory Proteins
• Biomarkers, Tumor
• HLA-A2 Antigen
• Interleukin-2
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• Interferon-gamma

Topics

• Antigens, CD (genetics, immunology, metabolism)
• Antigens, Neoplasm (immunology)
• Apoptosis Regulatory Proteins (genetics, immunology, metabolism)
• Biomarkers, Tumor (metabolism)
• CD8-Positive T-Lymphocytes
• Cell Proliferation
• HLA-A2 Antigen (metabolism)
• Humans
• Immunotherapy, Adoptive
• Interferon-gamma (metabolism)
• Interleukin-2 (immunology, metabolism)
• Lymphocyte Activation
• Lymphocytes, Tumor-Infiltrating (immunology)
• Melanoma (immunology, pathology)
• Programmed Cell Death 1 Receptor
• Skin Neoplasms (immunology, pathology)
• Tumor Cells, Cultured