Accumulation of myeloid-derived suppressor cells (MDSCs) diminishes antitumor immune responses necessary to control tumor growth and progression. MDSCs are discriminated from other monocytes in that they possess strong immunosuppressive activities rather than immunostimulatory properties. Exosomes are small membrane-bound vesicles that provide a method of communication between cells through their ability to transfer proteins and miRNA. We hypothesize that tumor cells secrete exosomes that are taken up by monocytes and promote MDSC differentiation through defective myeloid cell maturation.
Exosomes were isolated from tumor cell lines (osteosarcoma, glioma, colon carcinoma, melanoma, fibrosarcoma) and from primary cultures of each parental cell of origin. Following addition of exosomes to monocytes over 3 consecutive days, cells were collected for flow cytometry, transcriptional analysis, and T cell proliferation assays.
Increased expression of anti-inflammatory mediators (IL-10, iNOS, Arg1) and decreased expression of pro-inflammatory cytokines (IL-12, TNFa) was observed in the monocytes after the addition of exosomes from all the tumor lines supporting the conversion to a suppressor phenotype. Flow cytometry and T cell proliferation assays confirmed a MDSC phenotype. Exosomes isolated from the primary control cultures did not promote suppressive functions by the monocytes.
Our data supports the hypothesis that tumor-derived exosomes promote MDSC differentiation. A better mechanistic understanding of this interaction is critical for the discovery of novel therapeutic targets in cancer treatment, with the ultimate goal of preventing the conversion of monocytes to a suppressor phenotype.
Veterinary Medical Oncology Resident
University of Minnesota
Jennifer Lenz graduated veterinary school from the University of Wisconsin in 2014. She completed a rotating internship in small animal medicine and surgery at the University of Tennessee, and is currently a resident of small animal medical oncology at the University of Minnesota.
Thursday, June 14
5:30 PM – 5:45 PM
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