Targeting Tumor Metabolism to Enhance the Effectiveness of Antitumor Immune Response in the Treatment of Breast Cancer
Abstract
It has been well established that tumor cells escape immune detection through immunosuppressive networks and is one of the hallmarks of cancer. Down-regulation of surface antigen is one of the immunosuppressive mechanisms that enable cancer cells to escape immune detection. Among several antigens, shedding or cleavage of MIC [MHC class I Chain-related]-A or MIC-B surface antigens is frequently witnessed in cancer cells. Shedding of MICA and/ or MICB has been implicated in tumor progression and immune evasion. Since MICA/B shedding is an energy-dependent process, we hypothesized that targeting energy metabolism of cancer cells could delay or prevent the shedding process resulting in an increased expression of MICA/ B and better immune detection. This will enable us to enhance the antitumor immune-response. Data from the current research investigation demonstrate that human breast cancer cells pre-treated with low, non-toxic dose of the glycolytic inhibitor, 3-bromopyruvate (3-BrPA) show a better response to antitumor immunotherapy. One of the major implications of the current finding is that at low, non-cytotoxic dose antiglycolytic agent, 3-BrPA induces minimal perturbation of metabolism which is sufficient to block the shedding or cleavage of MICA and/ or MICB. The outcome of our study suggests that antiglycolytic pre-treatment sensitizes breast cancer cells to enhance the effectiveness of immunotherapeutics in the treatment of human breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2013
- Accession Number
- ADA599315
Entities
People
- Shanmugasundaram Ganapathy-kanniappan
Organizations
- Johns Hopkins University