Tumor Immunology

Asit K. De, PhD

Research Overview

Tumor Immunology

Breast cancer is one of the leading causes of cancer death in women. Development and improvement of the therapeutic strategies for management of breast cancer require better understanding of different mechanisms that might compromise therapies directed towards augmenting tumor specific immune responses. Intracellular expression of heat shock protein 27 (Hsp27), an important anti-apoptotic molecule belonging to the family of small molecular weight heat shock proteins, is reported as increased in human breast cancer cells and protects the tumor cells from radiation and different chemotherapeutic drugs. Recently, we have detected low levels of Hsp27 in the sera of healthy individuals by an ELISA developed in our laboratory. We have also demonstrated that soluble Hsp27 can significantly inhibit differentiation of human monocytes to dendritic cells (DC). DCs are most important cells for tumor antigen presentation, resulting in development of cytotoxic T lymphocytes (CTL) that are needed for killing the majority of cancer cells in the body. Based on the literature and our own data, we hypothesize that Hsp27 levels are increased in the serum of breast cancer patients. Increased serum Hsp27 levels may inhibit DC development leading to the generation of deficient CTLs in these patients. Such defective anti-tumor immune functions may eventually result in the faster progression of breast cancer cells. Our laboratory is extensively characterizing the immunoregulatory role of soluble Hsp27 on different leukocytes at the receptor, immunological, biochemical and molecular levels in the area of human breast cancer. Delineating this novel immunomodulatory role of soluble Hsp27 in breast cancer will lead to the appropriate design of different therapeutic approaches, particularly in the area of immunotherapy (e.g., dendritic cell vaccine).

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