Affiliations: [a] Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA | [b] University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA | National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Correspondence:
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Corresponding author: Wei-Zen Wei, Ph.D., Karmanos Cancer Institute, Wayne State University, 110 E. Warren Ave., Detroit, MI 48201, USA. Tel.: +1 313 833 0715, x 2360; Fax: +1 313 832 4537; E-mail: weiw@karmanos.org
Abstract: Different immune effectors control distinct steps in tumor metastasis; T cells inhibit the growth of primary and metastatic tumors, while NK control tumor cells in transit. Vaccination with DNA encoding Her-2 which is expressed on primary and metastasized breast cancer cells induced both humoral and cellular immunity to inhibit tumor growth. Vaccination efficacy can be amplified by depleting CD4+CD25+Foxp3+ regulatory T cells (Treg), but the risk of inducing autoimmunity warrants new strategies to selectively amplify anti-tumor immunity when modulating Treg. In the tumors, the major cyclooxygenase (COX)-2 product is prostaglandin E2(PGE2) which suppresses T and NK cells while amplifying Treg. These cellular responses to PGE2 are mediated through four E prostanoid (EP) receptors. Cox inhibitors and EP antagonists enhance NK activity to inhibit tumor metastasis; but they may down regulate MHC class I expression. Since T and NK cells have opposite requirements for MHC class I expression, their relative contribution to cancer control may vary with the stage of the disease. To enhance tumor infiltration by immune effectors, the role of CXCL9 is discussed. The complex nature of tumor metastasis necessitates a comprehensive approach to achieve successful immune intervention.
Keywords: Mouse mammary tumor, Her-2, regulatory T cells, cancer vaccine, cyclooxygenase, prostaglandin E2, NK cell
DOI: 10.3233/BD-2007-26110
Journal: Breast Disease, vol. 26, no. 1, pp. 115-127, 2007
