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Cancer Immunol Res. 2018 Jan 23. doi: 10.1158/2326-6066.CIR-17-0198. [Epub ahead of print]

CCL20 Expression by Tumor-Associated Macrophages Predicts Progression of Human Primary Cutaneous Melanoma.

Author information

1
Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. confocal@hggm.es paloma.sanchezmateos@salud.madrid.org.
2
Laboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
3
Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
4
Servicio de Cirugía General, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, Spain.
5
Servicio de Oncología, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, Spain.
6
Servicio de Dermatología, Hospital General Universitario Gregorio Marañón (HGUGM), Madrid, Spain.
7
Grupo de Inmuno-fisiología, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
8
Laboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. confocal@hggm.es paloma.sanchezmateos@salud.madrid.org.
9
Departamento de Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.

Abstract

The chemokine axis CCR6/CCL20 is involved in cancer progression in a variety of tumors. Here, we show that CCR6 is expressed by melanoma cells. The CCR6 ligand, CCL20, induces migration and proliferation in vitro, and enhances tumor growth and metastasis in vivo Confocal analysis of melanoma tissues showed that CCR6 is expressed by tumor cells, whereas CCL20 is preferentially expressed by nontumoral cells in the stroma of certain tumors. Stromal CCL20, but not tumoral CCR6, predicted poor survival in a cohort of 40 primary melanoma patients. Tumor-associated macrophages (TAM), independently of their M1/M2 polarization profile, were identified as the main source of CCL20 in primary melanomas that developed metastasis. In addition to CCL20, TAMs expressed TNF and VEGF-A protumoral cytokines, suggesting that melanoma progression is supported by macrophages with a differential activation state. Our data highlight the synergistic interaction between melanoma tumor cells and prometastatic macrophages through a CCR6/CCL20 paracrine loop. Stromal levels of CCL20 in primary melanomas may be a clinically useful marker for assessing patient risk, making treatment decisions, and planning or analyzing clinical trials. Cancer Immunol Res; 1-9. ©2018 AACR.

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