Heat Shock Proteins, Autoimmunity, and Cancer Treatment

Figure 2

Contrasting immunological influences of HSPs under differing contexts. We show that HSPs in cancer cells can inhibit or promote tumor immunity, depending on the tissue context. Tumor HSP levels become elevated during progression (blue line). This can lead to immune-suppressive effects of intracellular Hsp60 and Hsp70 as well as Hsp27, Hsp60, and Hsp70 secreted from tumor cells. However, if tumor cells are engineered to overexpress secretable forms of Grp78 or Gsp170 (purple line), antitumor immune response can be generated that are at least partially due to release of HSP tumor antigen complexes. In addition, necrotic killing of cells along with forced expression of Hsp70 (orange line) can lead to an inflammatory environment that triggers a tumor antigen-specific immune response.