Antigenic Hsp70–peptide upregulate altered cell surface MHC class I expression in TAMs and increases anti-tumor function in Dalton’s lymphoma bearing mice

• Published in: Tumor biology Vol. 36; no. 3; pp. 2023 - 2032
• Main Authors: Gautam, Pramod Kumar, Acharya, Arbind
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2015; Springer Nature B.V
• Subjects: Animals; Antigen presentation; Antigen Presentation - immunology; Antigens, Neoplasm - immunology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Communication - immunology; Female; Histocompatibility Antigens Class I - immunology; HSP70 Heat-Shock Proteins - immunology; Inflammation - immunology; Lymphoma; Lymphoma - immunology; Macrophages - immunology; Male; Mice; Mice, Inbred BALB C; Peptides; Protein expression; Research Article; Rodents; T-Lymphocytes, Cytotoxic - immunology; Up-Regulation - immunology; MHC class I (H2D; ); Hsp70–peptide complex; Tumor-associated macrophages; Tumor progression; Macrophage
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2809-9

Major histocompatibility complex (MHC) class I molecules not only provide a mechanistic framework for the cell-to-cell communication, but also possess broader biological function. Due to their ability to regulate presentation of tumor-associated antigens (TAAs), viral peptides which play an essential role in the regulation of immune responses by presenting antigenic peptides to cytotoxic T lymphocytes and by regulating cytolytic activities of immune cells. Tumor cells frequently do not express MHC class I molecules; as a result, tumor cells escape from immune surveillance. Cells surviving in tumor microenvironment are often characterized by a profound immune escape phenotype with alterations in MHC class I way of antigen processing. Cellular components of the tumor microenvironment, in particular alternatively activated M2 phenotype, are involved in tumor progression and suppression of anti-tumor immunity. Hsp70 is well recognized for its role in activating macrophages leading to enhanced production of inflammatory cytokines. It has been observed that Hsp70 derived from normal tissues do not elicit tumor immunity, while Hsp70 preparation from tumor cell associated with antigen are able to elicit tumor immunity. The finding shows that the expression of MHC class I (H2D b ) drastically decreases in TAMs and Hsp70–peptide complex enhances H2D b expression in TAMs and it reverts back the suppressed function of TAMs into the M1 state of immunoregulatory phenotype that promotes tumor regression by enhanced antigen presentation.