期刊
BRITISH JOURNAL OF CANCER
卷 112, 期 2, 页码 319-328出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.572
关键词
regulatory T cells; colorectal cancer; tumour immunology
类别
资金
- National Institute for Health Research (NIHR)
- Medical Research Council (MRC)
- Bowel Disease Research Foundation (BDRF)
- MRC [MR/J009962/1] Funding Source: UKRI
- Medical Research Council [MR/J009962/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10080] Funding Source: researchfish
Background: Regulatory T cells (Treg) are enriched in human colorectal cancer (CRC) where they suppress anti-tumour immunity. The chemokine receptor CCR5 has been implicated in the recruitment of Treg from blood into CRC and tumour growth is delayed in CCR5-/- mice, associated with reduced tumour Treg infiltration. Methods: Tissue and blood samples were obtained from patients undergoing resection of CRC. Tumour-infiltrating lymphocytes were phenotyped for chemokine receptors using flow cytometry. The presence of tissue chemokines was assessed. Standard chemotaxis and suppression assays were performed and the effects of CCR5 blockade were tested in murine tumour models. Results: Functional CCR5 was highly expressed by human CRC infiltrating Treg and CCR5(high) Treg were more suppressive than their CCR5(low) Treg counterparts. Human CRC-Treg were more proliferative and activated than other T cells suggesting that local proliferation could provide an alternative explanation for the observed tumour Treg enrichment. Pharmacological inhibition of CCR5 failed to reduce tumour Treg infiltration in murine tumour models although it did result in delayed tumour growth. Conclusions: CCR5 inhibition does not mediate anti-tumour effects as a consequence of inhibiting Treg recruitment. Other mechanisms must be found to explain this effect. This has important implications for anti-CCR5 therapy in CRC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据