ABSTRACT
Summary Searching for tumor-specific transplantation antigens for chemically induced tumors in rodents have led to uncovering the immunological properties of heat shock proteins (HSPs). Known best for their roles in protein folding and chaperoning, HSPs are now found to, (a) chaperone antigenic peptides, (b) modulate the functions of professional antigen presenting cells (APCs) and, (c) mediate presentation and cross-presentation of antigens to MHC molecules for T-cell activations. Thus, the roles of HSPs have extended beyond tumor immunity. This article summarizes the general immunological principles associated with HSPs. Features of specific HSPs including gp96, HSP90, HSP70, calreticulin (CRT), HSP110 and GRP170 are discussed in detail in the context of anti-tumor immune responses.
Introduction: discovery of HSPs in chaperoning anti-tumor immunity According to the concept of immunosurveillance first proposed by Burnet, one of the major functions of the adaptive immunity is to patrol and protect the host against malignancies due to the constant risk of somatic mutations and transformations (Burnet, 1970). Over the years, there has been a large collection of evidence for and against this theory. Nevertheless, it is increasingly appreciated that the immune system does play a critical role in the interaction between the host and malignancy. This is reinforced by the recent demonstration that an adequate immune system is critical in preventing the onset of clinically detectable tumors induced by carcinogens, or developed spontaneously (Shankaran et al., 2001). Therefore, understanding the mechanism of anti-tumor immune response is essential for generating immunotherapeutic approaches against cancer, and for realizing the dream that one day tumors can be prevented by a simple “shot” of tumor vaccines.
