Antigenic Hsp70–peptide upregulate altered cell surface MHC class I expression in TAMs and increases anti-tumor function in Dalton’s lymphoma bearing mice
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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 (H2Db) drastically decreases in TAMs and Hsp70–peptide complex enhances H2Db 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.
KeywordsMacrophage Tumor-associated macrophages MHC class I (H2Db) Hsp70–peptide complex Tumor progression
Hematopoietic stem cells
Heat shock protein
Peritoneal exudate cells
Major histocompatibility complex
We are thankful to Dr. S.S. Agarwal, IMS, BHU, Varanasi, for providing the flow cytometry facility for the analysis of receptors, Dr. S. C. Lakhotia, Department of Zoology, BHU, for immunofluorescence imaging. We are grateful to UGC, New Delhi for the student grants to PKG.
Conflict of interest
The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.
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