Modification of natural killer activity of lymphocytes infiltrating human lung cancers

The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxic activity and to determine its modulation by biologic agents. Local immunity may be an important component in limiting local tumor growth. Therefore, as a model for studying immune function in the local compartment, we assessed NK activity of lymphocytes present at the site of human tumors and in peripheral blood (PBL). We extracted tumor infiltrating lymphocytes (TIL) and PBL from patients with pulmonary tumors and compared NK activity and response to the biological modifiers gamma interferon (IFN-gamma), indomethacin (INDO), and interleukin 2 (IL-2). We also studied TIL and PBL LAK activity using the NK-resistant M14 target cells and determined the TIL response to IL-2, plus IFN-gamma. Titration of K562 targets in a 51Cr release assay revealed that untreated TIL have low cytotoxicity (4.32%) compared to untreated PBL (34.3%, P = less than 0.001). This low level of TIL NK activity was not affected by IFN-gamma, INDO, or IL-2 at 1 h. However, at 3 days of culture, IL-2 with or without exogenous IFN-gamma significantly increased TIL NK cytotoxicity (20.5%, P = 0.02 without IFN-gamma and 32.52 lytic units (LU), P = less than 0.02 with IFN-gamma). Untreated TIL and PBL both had low cytotoxicity against M14 targets (1.08 LU and 1.26 LU), respectively. After 3 days culture with IL-2 plus IFN-gamma, both TIL and PBL LAK cytotoxicity were increased (14.34 LU and 40.63 LU). We conclude that local NK and LAK activity is intrinsically low. However, this activity can be modulated by biologic agents, thus giving hope for the development of local anti-tumor effectors capable of in vivo tumor control.