Preoperative Local Immunotherapy with OK-432 (Picibanil) in Patients with Squamous Cell Cancer of the Oral Cavity

Abstract

Lymphocytes of normal experimental animals and human subjects are able to kill in vitro, without presensitization, a variety of virus-infected and tumor-derived target cells. This natural killer (NK) cell activity can be detected in peripheral blood (PB) as well as in lymphoid organs such as spleen, tonsils, lymph nodes (LN), and bone marrow of both rodents and human [1]. Recently a minor subpopulation of lymphocytes, according to their morphologic characteristics designated large granular lymphocytes (LGL), have been demonstrated to act as NK cells. It has been suggested that natural cytotoxicity plays an important role in immune surveillance against nascent tumors and virus infection in experimental animals and humans [2]. Furthermore, there is evidence that NK cells are actively involved in the destruction of circulating tumor cells and thus in the inhibition of hematogenous metastatic spread [2]. In cancer patients, especially in those with widely disseminated disease, NK cell activity has been found impaired in PB, suggesting that NK activity is influenced and/or regulated by tumor burden [4]. Assuming that NK cells are actively involved in defense mechanisms at the tumor site, one might expect high levels of NK activity in the peri- and intratumoral area as well as in the draining LN. However, lymphocytes isolated from human solid tumors and also from malignant exsudates have been found to express low or almost no NK activity. Similarly, lymphocytes derived from LN draining human tumors — breast, lung, and colon cancer — have been found to express variable levels of NK activity [3, 6].