Emerging evidence indicates a link between the increased proportion of regulatory T cells (Tregs ) and reduced survival in patients who have been diagnosed with
cancer. Cancer stem cells (CSCs) have been indicated to play a vital role in tumour initiation, drug resistance and recurrence. However, the relationship between Tregs and CSCs remains largely unknown. Here, we sorted out
ovarian cancer stem-like side population (SP) cells and CD133+ cells to investigate the influence of ovarian CSCs on Tregs . Among the various immune-related molecules that we assessed, C-C motif
chemokine ligand 5 (CCL5) was the most elevated in ovarian CSCs relative to that in the non-CSCs. The expression of its receptor, C-C motif
chemokine receptor 5 (CCR5), was also increased on the surface of Tregs in
ovarian cancer patients. This receptor-
ligand expression profile indicated that ovarian CSCs recruit Tregs via CCL5-CCR5 interactions. We further assessed the expression of
interleukin (IL)-10 in Tregs cultured with different
cancer cells. Tregs cultured in
conditioned medium (CM) from ovarian CD133+ cells expressed a higher level of
IL-10 than Tregs cultured in CM from CD133- cells, indicating that Tregs exert pronounced immune-inhibitory functions in CSC-rich environments. Furthermore, co-culture with
ovarian cancer cell lines induced the expression of
matrix metalloproteinase-9 (MMP9) in Tregs which, in turn, enhanced the degradation of the extracellular matrix and enabled the invasion of tumour cells, thereby facilitating tumour
metastasis. For the first time, to our knowledge, our findings describe the relationship between ovarian CSCs and Tregs , and demonstrated that these two cell populations co-operate to promote tumour immune tolerance and enhance tumour progression.