Immunotherapy of ovarian cancer with cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin: Effect of lymphadenectomy

The significance of lymphadenectomy in surgery for various kinds of cancer has been widely debated, particularly in the gynecological field. The cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin (BCG-CWS) has been used as an effective adjuvant for immunotherapy of a variety of cancer patients. Here we tested the immunological importance of lymph nodes in treatment of ovarian cancer patients with BCG-CWS. After surgical removal of tumors, 73 ovarian cancer patients were intracutaneously inoculated with BCG-CWS in the antigen-unloaded state in the upper arm at 4-week intervals at a dosage of 2-200 mu g. Significant correlation of lymphadenectomy and reduced survival of patients was observed (stages I, II, III, IV; hazard ratio 2.38, 95% confidence interval 1.02-5.12, Cox regression model). Lymphadenectomy also compromised with induction of interferon-gamma. In view of the importance of the role of lymph nodes in stimulation of Toll-like receptors by BCG-CWS, it is suggested that lymph nodes should be kept as much as possible to preserve the patient's immunity against cancer. Application of these results to surgery for other cancers should be considered. (Cancer Sci 2009; 100: 1991-1995).