Natural killer activity of lymphocytes infiltrating human lung cancers following preoperative systemic recombinant interleukin 2

T. M. Anderson, Y. Ibayashi, Y. Tokuda, S. Colquhoun, C. Holmes and S. H. Golub
Division of Surgical Oncology, UCLA School of Medicine 90024.

Tumor-infiltrating lymphocytes (TILs) show depressed natural killer (NK) activity compared with peripheral blood lymphocytes (PBLs). To determine if TIL NK function can be reactivated in vivo, 11 patients with tumors metastatic to the lung were treated with systemic recombinant interleukin 2 (rIL-2). Spontaneous TIL NK activity and NK activity after three days' incubation with 100 U/mL of rIL-2 were increased in patients receiving 15,000 U/kg of rIL-2 preoperatively compared with those receiving between 1000 and 10,000 U/kg. Histologically, higher doses of rIL-2 increased the number of intratumoral lymphocytes, the level of peritumoral lymphocytic transferrin, and the expression of HLA-DR. Spontaneous PBL NK activity in patients receiving between 10,000 and 15,000 U/kg of rIL-2 was also increased and was further increased by in vitro culture with rIL-2. Thus, PBL NK activity and TIL NK function in vivo can be augmented with 15,000 U/kg of systemic rIL-2. Both TIL- and PBL-inducible cytotoxicities were further enhanced by in vitro culture with rIL-2.