UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer

Berlato, C; Khan, MN; Schioppa, T; Thompson, R; Maniati, E; Montfort, A; Jangani, M; ... Balkwill, FR; + view all (2017) A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer. Journal of Clinical Investigation , 127 (3) pp. 801-813. 10.1172/JCI82976. Green open access

[thumbnail of Quezada_a CCR4_renal cancer.pdf]
Preview
Text
Quezada_a CCR4_renal cancer.pdf - Published Version

Download (1MB) | Preview

Abstract

Elevated expression of the chemokine receptor CCR4 in tumors is associated with poor prognosis in several cancers. Here, we have determined that CCR4 was highly expressed in human renal cell carcinoma (RCC) biopsies and observed abnormal levels of CCR4 ligands in RCC patient plasma. An antagonistic anti-CCR4 antibody had antitumor activity in the RENCA mouse model of RCC. CCR4 inhibition did not reduce the proportion of infiltrating leukocytes in the tumor microenvironment but altered the phenotype of myeloid cells, increased NK cell and Th1 cytokine levels, and reduced immature myeloid cell infiltrate and blood chemokine levels. In spite of prominent changes in the myeloid compartment, the anti-CCR4 antibody did not affect RENCA tumors in T cell–deficient mice, and treatment with an anti–class II MHC antibody abrogated its antitumor activity. We concluded that the effects of the anti-CCR4 antibody required the adaptive immune system and CD4+ T cells. Moreover, CCL17-induced IFN-γ production was reduced when Th1-polarized normal CD4+ T cells were exposed to the CCR4 ligand, evidencing the involvement of CCR4 in Th1/Th2 regulation. The anti-CCR4 antibody, alone or in combination with other immune modulators, is a potential treatment approach to human solid cancers with high levels of CCR4-expressing tumor-infiltrating leukocytes and abnormal plasma CCR4 ligand levels.

Type: Article
Title: A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/JCI82976
Publisher version: http://doi.org/10.1172/JCI82976
Language: English
Additional information: This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Keywords: Science & Technology, Life Sciences & Biomedicine, Medicine, Research & Experimental, Research & Experimental Medicine, REGULATORY T-CELLS, MULTICENTER PHASE-II, CHEMOKINE RECEPTOR 4, MACROPHAGE POLARIZATION, RECRUITMENT, EXPRESSION, CARCINOMA, MOGAMULIZUMAB, PROGRESSION, LYMPHOMA
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/1551038
Downloads since deposit
79Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item