Anti-tumor immunostimulatory effect of heat-killed tumor cells

• Published in: Experimental & molecular medicine Vol. 40; no. 1; pp. 130 - 144
• Main Authors: Yoon, Taek Joon, Kim, Ji Yeon, Kim, Hyojeong, Hong, Changwan, Lee, Hyunji, Lee, Chang-Kwon, Lee, Kwang Ho, Hong, Seokmann, Park, Se-Ho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2008; Springer Nature B.V; Korean Society of Medical Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Adjuvants, Immunologic; Animals; Antibodies, Neoplasm - immunology; Antibody Specificity - immunology; Antigens, Neoplasm - immunology; Biomedical and Life Sciences; Biomedicine; Cancer Vaccines - immunology; Cell Line, Tumor; Cell Proliferation; Cytokines - biosynthesis; Cytotoxicity, Immunologic - immunology; Dendritic Cells - immunology; Hot Temperature; Immunity, Cellular - immunology; Immunization; Immunologic Memory - immunology; Macrophages, Peritoneal - immunology; Medical Biochemistry; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Medicine; Neoplasms - immunology; Neoplasms - pathology; Original; Stem Cells; Survival Analysis; T-Lymphocytes, Cytotoxic - immunology; 생화학; interleukin 12; dendritic cells; cancer vaccines; mice; immunotherapy, active
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2008.40.1.130

AS a part of our ongoing search for a safe and efficient anti-tumor vaccine, we attempted to determine whether the molecular nature of certain tumor antigens would influence immune responses against tumor cells. As compared with freeze-thawed or formaldehyde-fixed tumor antigens, heat-denatured tumor antigens elicited profound anti-tumor immune responses and greatly inhibited the growth of live tumor cells. The heat-denatured tumor antigens induced a substantial increase in the anti-tumor CTL response in the absence of any adjuvant material. This response appears to be initiated by strong activation of the antigen-presenting cells, which may recognize heat-denatured protein antigens. Upon recognition of the heat-denatured tumor antigens, macrophages and dendritic cells were found to acutely upregulate the expression of co-stimulatory molecules such as B7.2, as well as the secretion of inflammatory cytokines such as IL-12 and TNF-α. The results of this study indicate that heat-denatured tumor extracts might elicit protective anti-tumor adaptive immune responses and also raise the possibility that a safe and efficient adjuvant-free tumor vaccine might be developed in conjunction with a dendritic cell-based tumor vaccine.