Exosomes can activate myeloid-derived suppressor cells via interaction of membrane heat shock protein 70 (HSP70) with Toll-like receptor 2 (TLR2) on the myeloid-derived suppressor cell. As reported in the Journal of the National Cancer Institute, Gobbo and colleagues found that the A8 peptide aptamer could be used to bind to the extracellular domain of membrane HSP70 and capture HSP70 exosomes from cancer patient samples.
In studies involving breast, lung, and ovarian cancer patient samples and cultured cells, it was found that the number of HSP70 exosomes was higher in cancer patients than in healthy donors (mean = 3.5 vs 0.17 ng/mL, P = .004) and that exosomes were released by all cancer cell lines but not by normal cells. HSP70 exhibited greater affinity for A8 than for TLR2, with A8 blocking the association of HSP70 with TLR2 and inhibiting the ability of tumor-derived exosomes to activate myeloid-derived suppressor cells.
Treatment of tumor-bearing C57Bl/6 mice with A8 resulted in a reduced number of myeloid-derived suppressor cells in the spleen and inhibition of tumor progression. Exposure to cisplatin and fluorouracil (5-FU) increased the amount of HSP70 exosomes, supporting activation of myeloid-derived suppressor cells and inhibiting the development of an antitumor immune response. When cisplatin or 5-FU was combined with A8, such myeloid-derived suppressor cell activation was not observed, and the antitumor effect of the drugs was enhanced.
The investigators concluded:
“A8 might be useful for quantifying tumor-derived exosomes and for cancer therapy through myeloid-derived suppressor cell inhibition.”