ONCOLYTIC ACTIVITY OF NK CELLS AGAINST SW-756 SQUAMOUS CERVICAL-CARCINOMA CELL-LINE - ROLE OF INTERFERON-ALPHA ALPHA AND GAMMA AND CD54 ADHESION MOLECULE IN ONCOLYSIS

We investigated the sensitivity of a cervical tumor cell line SW-756 t o lysis by peripheral blood mononuclear cells (MNC), natural killer (N K) cells, and major histocompatibility complex (MHC)-nonrestricted (MH C-NR) T cells from cervical cancer patients and normal donors. We foun d that SW-756 was resistant to lysis mediated by naive (unstimulated) MNC and MHC-NR T cells, but sensitive to lysis by naive NK cells. Howe ver, the cytotoxic function of MNC could be activated with interleukin -2 (IL-2) and interferon (IFN) alpha or gamma. Although IFNs were effe ctive in enhancement of effector cell cytotoxicity and inhibited proli feration of cervical tumor cells, they also exerted an adverse effect on cytotoxicity; specifically, pretreatment of SW-756 cells with IFNs significantly decreased their susceptibility to lysis by effector cell s. Analysis of surface phenotype of SW-756 cells after treatment with IFNs showed up-regulation of expression of HLA class I determinants, t he phenomenon that may be responsible for decreased sensitivity of thi s tumor to MHC-NR NK cells. The studies on the involvement of CD54 adh esion molecule in cytotoxic functions indicated that expression of thi s molecule on effector cells (but not on target cells) was important f or cytotoxicity against SW-756 tumor celts. The therapeutic implicatio n of these studies for patients with cervical cancer is discussed. (C) 1994 Academic Press, Inc.