The role of tumour-expressed CCR6 and CCR7 in breast cancer metastasis and tumour immunity

Abstract

This project aims to investigate the role of tumour-expressed CCR6 and CCR7 in breast cancer metastasis and in the anti-tumour immune response in the lymph node. EO771 murine breast cancer cell-line was modified to express the CCL20 chemokine receptor CCR6 or a receptor for the chemokine CCL21, CCR7. Data support that CCR6 can mediate survival signals in human breast cancer cells, while CCR7 is known to drive lymph node tumour metastasis. Constitutive expression of CCR6 and CCR7 in modified EO771 was confirmed in vitro and in vivo. Neither CCR6 nor CCR7 upregulation, with and without ligand addition significantly affected cell proliferation or apoptosis in normal culture conditions. Preliminary studies with the CCR7+ EO771 in vivo showed promoted metastasis to tumour-draining lymph nodes, with 80% of the analysed samples forming tumour foci in the B-cell area. Immunofluorescence analyses detected regulatory T-cells within all tumour foci analysed and indicated that PD-L1 was upregulated in T-cell areas close to the tumour foci. The latter observations suggest that metastasizing tumour cells alter the anti-tumour response. In summary, the present study lay a foundation for future research elucidating the roles of tumour-expressed CCR6 and CCR7 in lymph node metastasis, tumour survival and anti-tumour immunity.