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      저자 : ( Kyung Hwan Kimv ) (검색결과 1 건)
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      • T-Cell Exhaustion Determined by PD-1 Expression on Tumor-Infiltrating CD8 T-Cells in Hepatocellular Carcinoma

        ( Shin Hwang ),( Hyung-don Kim ),( Su-hyung Park ),( Gi-won Song ),( Seongyeol Park ),( Min Kyung Jung ),( Kyung Hwan Kimv ),( Sukyeong Eo ),( Deok-bog Moon ),( Young Seok Ju ),( Eui-cheol Shin ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Aims: Phenotypic and functional characteristics of tumor-infiltrating CD8 T-cells (CD8 TILs) has not been well studied in the context of heterogeneity of exhausted T-cells and patient stratification in hepatocellular carcinoma (HCC). Methods: We identified distinct T-cell exhaustion profiles determined by PD-1 expression levels on CD8 TILs from 48 HCC patients undergoing surgical resection by multi-color flow cytometry and RNA sequencing. Results: CD8 TILs from HCC patients significantly overexpressed immune checkpoint receptors such as PD-1, TIM-3 and LAG-3. CD8 TILs could be further stratified into PD-1<sup>hi</sup>, PD-1<sup>int</sup> and PD-1<sup>neg</sup> subpopulations, and TIM-3 and/or LAG-3 were exclusively expressed on PD-1<sup>hi</sup>, not PD-1<sup>int</sup>, subpopulation. RNA expression profiles were distinct among PD-1<sup>hi</sup>, PD-1<sup>int</sup> and PD-1<sup>neg</sup> CD8 TILs and a gene module of T-cell exhaustion was significantly enriched in PD-1<sup>hi</sup> CD8 TILs. HCC patients could be classified into two distinct subgroups based on the proportion of PD-1<sup>hi</sup> CD8 TILs; High PD-1 expressers and Low PD-1 expressers. High PD-1 expressers had more severely dysfunctional CD8 TILs with exhaustion profiles that were observed in PD-1<sup>hi</sup> CD8 TILs, compared to Low PD-1 expressers. High PD-1 expressers were associated with aggressive biologic tumor features. Combination blockades of Tim-3 or LAG-3 in addition to PD-1 blockade further enhanced proliferative responses of CD8 TILs from High PD-1 expressers. Conclusions: CD8 TILs displayed heterogeneous exhaustion profiles determined by differential PD-1 expression levels in HCC patients. A certain subgroup of HCC patients expressing multiple immune checkpoint receptors appears to be eligibly indicated for immune checkpoint inhibitors for effective reinvigoration of anti-tumor immunity.

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