Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4873K) PDF+supp data (5948K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Kuang, D.-M. Articles by Zheng, L. PubMed PubMed Citation Articles by Kuang, D.-M. Articles by Zheng, L. Social Bookmarking                            What's this?

¹ State Key Laboratory of Biocontrol, ² Department of Immunology, and ³ State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University, Guangzhou 510 275, China

CORRESPONDENCE Limin Zheng: zhenglm{at}mail.sysu.edu.cn

Macrophages (M) are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of M to trigger transient activation of monocytes in peritumoral stroma. We showed that a fraction of monocytes/M in peritumoral stroma, but not in cancer nests, expresses surface PD-L1 (also termed B7-H1) molecules in tumors from patients with hepatocellular carcinoma (HCC). Monocytes activated by tumors strongly express PD-L1 proteins with kinetics similar to their activation status, and significant correlations were found between the levels of PD-L1⁺ and HLA-DR^high on tumor-infiltrating monocytes. Autocrine tumor necrosis factor and interleukin 10 released from activated monocytes stimulated monocyte expression of PD-L1. The PD-L1⁺ monocytes effectively suppressed tumor-specific T cell immunity and contributed to the growth of human tumors in vivo; the effect could be reversed by blocking PD-L1 on those monocytes. Moreover, we found that PD-L1 expression on tumor-infiltrating monocytes increased with disease progression, and the intensity of the protein was associated with high mortality and reduced survival in the HCC patients. Thus, expression of PD-L1 on activated monocytes/M may represent a novel mechanism that links the proinflammatory response to immune tolerance in the tumor milieu.

Abbreviations used: DFS, disease-free survival; HCC, hepatocellular carcinoma; MFI, mean fluorescence intensity; M, macrophages; NOD/SCID, nonobese diabetic/severe combined immunodeficiency; OS, overall survival; rh, recombinant human; TSN, tumor culture supernatant.

© 2009 Kuang et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS