B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders

B7-H1(PD-L1、CD274)在T细胞淋巴增殖性疾病中抑制宿主免疫。

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作者:Ryan A Wilcox ,Andrew L Feldman, David A Wada, Zhi-Zhang Yang, Nneka I Comfere, Haidong Dong, Eugene D Kwon, Anne J Novak, Svetomir N Markovic, Mark R Pittelkow, Thomas E Witzig, Stephen M Ansell

Abstract

Stromal elements present within the tumor microenvironment may suppress host immunity and promote the growth of malignant lymphocytes in B cell-derived non-Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's role in T cell-derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of costimulatory/co-inhibitory ligands expressed by both malignant cells and stromal cells within the tumor microenvironment, has emerged as an important immune modulator capable of suppressing host immunity. Therefore, B7-H1 expression and function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and promote the induction of FoxP3(+) regulatory T cells. Collectively, the data presented provide the first evidence implicating B7-H1 in the suppression of host immunity in T-cell lymphoproliferative disorders and suggest that the targeting of B7-H1 may represent a novel therapeutic approach.

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