The immunology and immunotherapy of breast cancer: an update

Adenocarcinomas of the breast behave clinically and epidemiologically in wa ys that show host resistance factors are important for outcome in addition to grade and stage of malignancy. Immune reactivity to autologous tumors is indicated by the general presence of lymphoid infiltration (LI) and region al lymph node changes; however, these changes predict favorable outcome onl y in non-metastatic disease. LI is characterized by CD4(+) and CD8(+) tumor infiltrating lymphocytes reflecting latent cell-mediated immunity (CMI). C MI and humoral immune reactivity have been demonstrated to autologous tumor and a variety of tumor-associated antigens (TAA) have been implicated incl uding CEA, HER-2/neu, MAGE-1, p53, T/Tn and MUC-1. Immune incompetence invo lving CMI is progressive with the stage of breast cancer and is prognostica lly significant. Immunotherapy of several types has been designed to addres s this immunodeficiency and the TAAs involved. Animal models have employed drug therapy, cytokine transfection, vaccines w ith autologous tumor, cytokines like interferon alpha (IFN-alpha) and inter leukin-2 (IL-2), TAA tumor vaccines, and immunotoxins with evidence of tumo r regression by immunologic means. Immunotherapy of human breast cancer is a rapidly growing experimental area . Positive results have been obtained with natural IFN and interleukins, pa rticularly in combination strategies (but not with high dose recombinant IF N or IL-2), with autologous tumor vaccine (but not yet with transfected aut ologous tumor); with a mucin carbohydrate vaccine (Theratope(TM)) in a comb ination strategy (but not with mucin core antigen) and with several immunot oxins. Combination strategies involving immunorestoration, contrasuppressio n, adjuvant, and immunotoxins are suggested for the future. (C) 1999 Intern ational Society for Immunopharmacology. Published by Elsevier Science Ltd.