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期刊名称: BLOOD CANCER JOURNAL
Volume:5    Issue:2        Page:e281-e281
ISSN:2044-5385

PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival期刊论文

作者: Yang ZZ Grote DM Ziesmer SC Xiu B Novak AJ
DOI:10.1038/bcj.2015.1

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页码: e281-e281
被引频次: 56
出版者: NATURE PUBLISHING GROUP,Springer Nature B.V
期刊名称: BLOOD CANCER JOURNAL
ISSN: 2044-5385
卷期: Volume:5    Issue:2
语言: English
摘要: To determine the biological and clinical relevance of programmed death 1 (PD-1) in follicular lymphoma (FL), we characterized PD-1(+) T-cell subsets and assessed their biological function as well as potential clinical impact. We found that PD-1 is expressed on intratumoral CD4(+) T cells with both bright and dim intensity, representing two different sub-populations of cells. By immunohistochemistry, we found that CD4(+) PD-1(high) T cells predominantly reside in the lymph node follicles, while PD-1(low) T cells are mainly located in an interfollicular pattern. Intratumoral CD4(+) PD-1(high) T cells have a T-FH cell phenotype, express CXCR5, secrete IL-21 and are BCL-6 positive with no TIM-3 expression. In contrast, CD4(+) PD-1(low) T cells have an exhausted phenotype, express TIM-3 and do not express BCL-6 and CXCR5. Functionally, CD4(+) PD-1(high) T cells actively supported B-cell growth, while CD4(+) PD-1(low) T cells displayed a reduced cytokine production and cell-signal transduction. Clinically, we observed that the numbers of CD4(+) or CD8(+) PD-1(low) T cells significantly correlate with a reduced overall survival in FL patients (P = 0.007 and 0.04 respectively; n = 32). In contrast, the number of CD4(+) PD-1(high) T cells was not associated with patient outcome. Taken together, these results indicated that PD-1 expression defines two sub-populations with distinct functions that differentially impact patient outcome in FL.
相关主题: CXC CHEMOKINE RECEPTOR-5, TRANSFORMATION, HIGH NUMBERS, ONCOLOGY, NON-HODGKINS-LYMPHOMA, TIM-3, EXHAUSTION, LYMPHOCYTES, Lymph Nodes - pathology, Lymphoma, Follicular - pathology, Humans, Middle Aged, Gene Expression Regulation, Neoplastic, Lymph Nodes - metabolism, Male, CD4-Positive T-Lymphocytes - pathology, CD4-Positive T-Lymphocytes - immunology, Lymphoma, Follicular - epidemiology, Flow Cytometry, Lymphoma, Follicular - genetics, T-Lymphocyte Subsets - pathology, T-Lymphocyte Subsets - metabolism, Programmed Cell Death 1 Receptor - biosynthesis, Survival Analysis, Aged, 80 and over, Adult, Female, Aged, Neoplasm Staging, Programmed Cell Death 1 Receptor - genetics, Index Medicus,

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