The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer.
The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer.
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DOI：
10.1038/bjc.2014.572
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发表时间：
2015-01-20
影响因子：
8.8
通讯作者：
Adams DH
中科院分区：
文献类型：
--
作者：
Ward ST;Li KK;Hepburn E;Weston CJ;Curbishley SM;Reynolds GM;Hejmadi RK;Bicknell R;Eksteen B;Ismail T;Rot A;Adams DH
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. 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. Functional CCR5 was highly expressed by human CRC infiltrating Treg and CCR5high Treg were more suppressive than their CCR5low 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. 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.
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DOI：
10.4049/jimmunol.182.1.171
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Camargo JF;Quinones MP;Mummidi S;Srinivas S;Gaitan AA;Begum K;Jimenez F;VanCompernolle S;Unutmaz D;Ahuja SS;Ahuja SK
通讯作者：
Ahuja SK
影响因子：
11.2
作者：
Chang, Li-Yuan;Lin, Yung-Chang;Lin, Chun-Yen
通讯作者：
Lin, Chun-Yen
影响因子：
5.3
作者：
Kuziel, WA;Dawson, TC;Maeda, N
通讯作者：
Maeda, N
影响因子：
2.2
作者：
Ford, AL;Foulcher, E;Sedgwick, JD
通讯作者：
Sedgwick, JD
影响因子：
11.2
作者：
Gobert, Michael;Treilleux, Isabelle;Menetrier-Caux, Christine
通讯作者：
Menetrier-Caux, Christine