Oncolytic activity of NK cells against SW-756 squamous cervical carcinoma cell line: role of interferons alpha and gamma and CD54 adhesion molecule in oncolysis.
We investigated the sensitivity of a cervical tumor cell line SW-756 to lysis by peripheral blood mononuclear cells (MNC), natural killer (NK) cells, and major histocompatibility complex (MHC)-nonrestricted (MHC-NR) T cells from cervical cancer patients and normal donors. We found 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. However, the cytotoxic function of MNC could be activated with interleukin-2 (IL-2) and interferon (IFN) alpha or gamma. Although IFNs were effective in enhancement of effector cell cytotoxicity and inhibited proliferation 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 cells. Analysis of surface phenotype of SW-756 cells after treatment with IFNs showed up-regulation of expression of HLA class I determinants, the phenomenon that may be responsible for decreased sensitivity of this tumor to MHC-NR NK cells. The studies on the involvement of CD54 adhesion molecule in cytotoxic functions indicated that expression of this molecule on effector cells (but not on target cells) was important for cytotoxicity against SW-756 tumor cells. The therapeutic implication of these studies for patients with cervical cancer is discussed.
Cristoforoni
P M
PM
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Lotzová
E
E
Cook
K R
KR
Chuang
L T
LT
Morris
M
M
Grossi
C E
CE
Wharton
J T
JT
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007372:Interferons / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D007372:Interferons