期刊
JOURNAL OF IMMUNOTHERAPY
卷 33, 期 9, 页码 956-964出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e3181fad2b0
关键词
PD-1; PD-L1; TIL; tumor immunity; melanoma; tumor digest; tumor microenvironment
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-gamma 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.
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