Relationships between susceptibility to LAK cell-mediated lysis, conjugate formation and expression of adhesion molecules in B-cell derived non-Hodgkin's lymphomas.
Adoptive immunotherapy with LAK cells has been investigated for the treatment of B-cell-derived lymphomas, but only a few significant tumor regressions were obtained. In order to explain this refractory state, the sensitivity to normal LAK-mediated lysis of 30 non-Hodgkin's lymphoma (NHL) malignant B-cells was determined using flow cytofluorimetry. A large heterogeneity was found, and we report a close correlation (p < 0.001) between the extent of lysis of malignant B-cells and their ability to form conjugates with LAK cells; which is the first step in LAK-mediated cytolysis. The levels of expression of HLA class I molecules, LFA-1 (CD11a/CD18), CD54 and CD58 were also studied and found to be expressed very heterogeneously. CD54 expression on malignant B-cells plays a major role in the initial conjugate formation with LAK cells (p < 0.001), and this was confirmed by inhibition experiments. Our results suggest that a weak expression of CD54 could constitute one mechanism by which NHL tumor B-cells escape natural immune surveillance and resist LAK cells immunotherapies.
Chaperot
L
L
Laboratoire d'Immunologie ETS Isère et Savoie BP, La Tronche, France.
Jacob
M C
MC
Le Vacon
F
F
Giroux
C
C
Molens
J P
JP
Sotto
J J
JJ
Bensa
J C
JC
Plumas
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018968:CD58 Antigens / Q000096:biosynthesis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D018968:CD58 Antigens; D015395:Histocompatibility Antigens Class I; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1