The present disclosure relates to synthetic alpha-galactosyl ceramide (&alpha；-GalCer) analogs, and their use as immunotherapies. In one aspect. a method of activating a cytokine response in a subject includes administering an effective amount of a compound to a subject, wherein the subject has an adaptive immune system that includes a population of cells, the population including at least one lymphocyte and at least one antigen-presenting cell, and wherein the compound is represented by the structure of formula 1: or a pharmaceutically acceptable salt thereof； forming a complex between the compound and the antigen-presenting cell, wherein the formation of the complex results in the activation of a receptor on the lymphocyte； and activating the lymphocyte to produce the cytokine response.
