Prospects of controlling breast cancer metastasis by immune intervention.
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.
Fulton
Amy
A
University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Miller
Fred
F
Weise
Amy
A
Wei
Wei-Zen
WZ
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology / Q000517:prevention & control; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D019496:Cancer Vaccines; D015232:Dinoprostone; D018719:Erb-b2 Receptor Tyrosine Kinases