Chapter 22 - Immune Response to Tumor Stress Proteins—Implications for Vaccine Development Against Cancer

Abstract

Stress proteins or heat shock proteins (HSP) belong to the most conserved proteins. The conservation of stress proteins stems from their basic and vital role in cells: Prevention of protein aggregation under stress and physiological conditions. Stress proteins are important target antigens in autoimmune diseases and during certain bacterial infections. This chapter reviews the immunogenicity of stress proteins of tumor cells, stimulation of T cell response by tumor stress proteins and implications this Tcell response have for immunity against the tumor or autoimmunity. The expression of stress proteins in cancer is altered. An overexpression of constitutively expressed or inducible stress proteins of HSP 70, HSP 90, and gp96 stress proteins on the cell surface of tumor cells is reported. The chapter describes the correlation between the immunogenicity and stress protein expression of tumors. These correlation observations suggest the implication of tumor stress protein for vaccine development against cancer. There is comprehensive experimental evidence that tumor-derived stress protein preparations are effective as autologous tumor vaccines. Stress proteins HSP 70 and 90 in the cytoplasm, and gp96 in the endoplasmic reticulum (ER) are complexed with endogenous tumor peptide antigens. These are channeled into the MHC class I restricted antigen presentation pathway and presented on the surface of APC by MHC class I molecules towards CD5 positive T cells. In context of costimulatory signals and a supportive cytokine milieu, tumor-specific CD5 positive T cells are efficiently activated and develop to tumor-specific cytotoxic T lymphocytes, which can lyse the tumor cells.