Editorial: HSPs—Ambiguous Mediators of Immunity

Specialty section: This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology Editorial on the Research Topic HSPs—Ambiguous Mediators of Immunity Heat shock proteins (HSPs) were discovered as polypeptides induced by stress that can be found in all kingdoms of cellular organisms. Their functions were, a first enigmatic and these proteins were thus classified by molecular weight, as in—Hsp27, Hsp70, Hsp90, Hsp110 (1). More recently, each of these size-classified molecules has attributed a role in protein folding, and they thus came to be known, as a class, as molecular chaperones—deterrents of unsuitable interactions between intracellular proteins (2). However, the HSPs possess properties beyond chaperoning. Indeed, their discovery in the extracellular spaces suggested roles in intercellular signaling and in the convoluted regulation of the immune responses. A number of lines of investigation triggered interest in HSPs as mediators of immunity. Srivastava and others found that the molecular chaperone properties of HSPs could be harnessed in cancer vaccine design (3–5). They emphasized the role of HSPs in capturing tumor antigens and permitting their uptake and processing by antigen-presenting cells (APCs) prior to activation of cytotoxic lymphocytes. Others suggested that HSPs could behave like endogenous danger signals when flooding into the extracellular microenvironment after cell death (6). In another line of investigation, investigators studied the role of mycobacterial Hsp65 and Hsp70 in suppression of autoimmune diseases such as arthritis, diabetes, and prolongation of tissue grafts [Borges et al.; (7, 8)]. HSPs were thus implicated in contrasting and apparently opposed aspects of immunity. The current volume contains articles dealing with these aspects of HSP biology. Four articles describe various roles of HSPs in tumor immunity and anticancer vaccine construction. In chapter 1, Zuo et al. describe tumor immunity strategies built around the " large HSPs " —Hsp110 and GRP170. These larger HSPs possess chaperoning power of remarkable strength leading to high avidity for antigens and effective vaccines. Shevtsov and Multhoff in chapter 4 review in detail Hsp70 and Hsp90 vaccines and their effectiveness in tumor therapy. The biological properties of Hsp90 are further discussed in chapter 5 by Tamura et al., emphasizing the role of this molecule in permitting antigens to cross plasma membranes, enter cells by endocytosis and cross the endosomal wall to the sites of antigen processing and acquisition by MHC Class I molecules. Most studies have indicated a role for surface receptors in mediating …