OK-432-induced enhancement of ICAM-1 expression on tumor cells positively correlates to therapeutic effects for malignant effusion.

The intracavitary injection of OK-432 has been shown to be an effective immunotherapy for patients with malignant effusion. We investigated the contribution of intercellular adhesion molecule-1 (ICAM-1) on the surface of tumor cells to its therapeutic effect. We treated 13 patients with malignant effusion with OK-432. Tumor cells were freshly isolated from effusion samples obtained before and 24 hr after initiation of the therapy. Surface expression of ICAM-1 was analyzed by flow cytometry and its relation to the therapeutic effect was analyzed. An objective clinical response was observed in 7 (53.8%) of 13 patients. Following OK-432 injection, ICAM-1 levels showed an average of 5.73-fold increase in clinical responders (7 patients), whereas no increase in nonresponders (6 patients). ICAM-1 expression more than doubled after therapy in 7 patients, 6 of whom showed a clinical response. Survival was significantly prolonged in these patients compared with that in the 6 patients in whom ICAM-1 levels did not double after therapy. Only 1 of the 6 patients in whom ICAM-1 levels did not double showed a clinical response. Pretherapeutic ICAM-1 expression was not significantly correlated with the subsequent clinical effect. OK-432 injection was associated with an increase in surface expression of ICAM-1 on tumor cells. This increased ICAM-1 expression was positively correlated with therapeutic effect, suggesting that ICAM-1 expression on tumor cells may be a useful marker for evaluation of efficacy of OK-432 therapy.