Combined Nutritional and Immunological Intervention to Activate Natural Cytotoxicity Against Breast Cancer Cells in Vitro and in Vivo

摘要

The hypothesis of this Idea Award is that a combination of nutritional and immunological treatments may be effective in stimulating the body's natural immune defenses against breast cancer. Specifically, the project is examining whether retinoic acid (RA), a metabolite of vitamin A shown to modulate the differentiation and/or activation of several types of immune cells, and alpha-galactosylceramide (alpha-GalCer), a synthetic lipid known to alter immune function and to exert antitumorigenic activity, will reduce the growth and/or stimulate natural immunity against 4T1 tumors in adult female Balb/C mice inoculated with 4T1 syngenic breast tumor cells. Natural immunity might help to fight the tumor. In year 3, we have injected 4T1 breast tumor cells intravenously to simulate hematogenous diffusion and have examined the immune system response, micro-metastases, and the expression of Matrix Metalloproteinase (MMP) genes that may be involved in the metastasis to the lungs. We found that in vivo treatment with RA and alpha GalCer reduced the number of micro-metastases, and reduced expression of certain MMP mRNAs, especially MMP3. Treatment also resulted in systemic changes in immune system cells which included enrichment of CD11b-positive myeloid cells, of which granulocytes (GR1-positive cells) are the dominant type. The results to date support the idea that a nutritional and immunological combination treatment in vivo could be effective in reducing the growth and metastasis of breast tumor cells.