The present invention provides compositions and methods that involve the 36 kDa annexin II monomer, which has been identified as having immunostimulatory properties. Accordingly, in one aspect, the invention provides compositions that include at least one 36 kDa annexin II monomer or an immunomodulatory fragment thereof. In another aspect, the invention provides methods that include administering to a subject a composition that includes at least one 36 kDa annexin II monomer or an immunomodulatory fragment thereof. In another aspect, the invention provides methods that induce an in situ increase in the 36 kDa annexin II monomer by administering to a subject an amount of composition effective to induce localized hypoxia sufficient to cause a localized increase in annexin II.