Fucosylation and immune surveillance in melanoma
View Patent ↗Disclosed are methods for treating a cancer and/or enhancing immune responses to infiltration of tumors comprising administering to a subject a fucose. Also disclosed herein are methods of detecting the presence of a sugar-modified protein (i.e., a glycosylated protein).
1. A method of enhancing an immune response in a subject with a tumor, wherein the subject is administered D-fucose, fucose-1-phosphate, or GDP-L-fucose to increase fucosylation and thereby increase the number of tumor infiltrating lymphocytes by at least 10-fold.
2. The method of claim 1 , wherein the fucose is administered orally.
3. The method of claim 1 , wherein the lymphocytes are NK cells, dendritic cells, or T cells.
4. The method of claim 1 , wherein the method further results in at least a 20% reduction in myeloid-derived suppressor cells.
5. A method of treating a cancer in a subject comprising administering to the subject D fucose, fucose-1-phosphate, or GDP-L-fucose and an anti-tumor agent.
6. The method of treating a cancer of claim 5 , wherein the anti-tumor agent is an immune checkpoint blockade inhibitor.
7. The method of treating a cancer of claim 6 , wherein the immune checkpoint blockade inhibitor is selected from the group consisting of the PD-1 inhibitors lambrolizumab, Nivolumab, pembrolizumab, and/or pidilizumab; the PD-L1 inhibitors BMS-936559, Atezolizumab, Durvalumab, and/or Avelumab; and/or the CTLA-4 inhibitor ipilimumab.
8. The method of treating a cancer claim 5 , wherein the fucose is administered orally.
9. The method of treating a cancer of claim 5 , wherein the fucose is administered before and/or during administration of the anti-tumor agent.