Heat shock proteins exist in all cells and are necessary for their survival. The induction of HSP gene expression is triggered in stressful conditions, with heat shock being the most important one. Their protective role in cells facilitates survival and tumor progression by protecting these altered cells from death. When HSP is released from the cell during necrosis or by vesicles, these chaperones take on a new role as drivers of anti-tumor immunity. By binding independently to macrophage receptors, they take on the role of danger signals and initiate an inflammatory response and macrophage activation, which leads to the capture and destruction of tumor cells. Released HSPs can also form complexes with other released tumor antigens, facilitating their uptake by antigen-presenting cells. Dendritic cells process the antigens taken up within these complexes and present them with MHC-I molecules to naïve CD8+ T cells. This process of cross-presentation initiates an adaptive immune response, including the cytotoxic actions of T cells. The mechanism by which CTLs destroy tumor cells depends on membrane-bound HSP70 on the target cell, which enhances the entry of the pro-apoptotic enzyme granzyme B. Membrane-bound HSP also enables natural killer cells to kill tumor cells that have evaded T cell attack, thereby enhancing the overall anti-tumor response.