Oxaliplatin resistance is a challenge in the treatment of colorectal cancer patients. Regulatory T cells (Tregs) are well known for their immunosuppressive roles and targeting Tregs is an effective way to improve chemosensitivity. Exosome delivered miRNA might be used as a potential biomarker for predicting the chemosensitivity. However, the relationship between Tregs and exosomal miRNAs remain largely unknown. A mouse xenograft model was adopted to evaluate the correlation between exosome-derived miR-208b and Tregs in vivo. We demonstrated that circulating miR-208b is a non-invasive marker for predicting FOLFOX sensitivity in colorectal cancer. miR-208b in the colon cancer was secreted by the tumor cells in the pattern of exosomes, and oxaliplatin resistant cells showed the most obvious phenomenon of miR-208b increase. Colon cancer cells-secreted miR-208b was sufficiently delivered into recipient T cells to promote Tregs expansion by targeting programmed cell death factor 4 (PDCD4). Furthermore, in vivo studies indicated that Tregs expansion mediated by cancer cell-secreted miR-208b resulted in tumor growth and oxaliplatin resistance. Our results demonstrate that tumor-secreted miR-208b promotes Tregs expansion by targeting PDCD4 and it may be related to decrease of oxaliplatin-based chemosensitivity in CRC.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.