Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors

Abstract

The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B-CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B- CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL-2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings.

Expansion of cytotoxic effectors with lytic activity against autologous blasts from acute myeloid leukaemia patients in complete haematological remission

“…These results, together with the evidence that effective LAK cells may be generated from leukaemic patients in disease remission (Lauria et al, 1994), are in contrast to the defective killing capacity of LAK effectors generated from AML patients at diagnosis (Foa et al, 1991a). T and cytotoxic cells in®ltrating or associated with solid and haematological malignancies present several functional defects in molecules involved in the triggering of effector functions (Tursz et al, 1982;Ruco et al, 1983;Frydecka, 1985;Foa et al, 1990;Nakagomi et al, 1993;Lai et al, 1996;Kono et al, 1996); these abnormalities may be secondary to the presence of the tumour (Whiteside, 1999) and are usually reversible after activation of these effectors Renner et al, 1996).…”

Expansion of cytotoxic effectors with lytic activity against autologous blasts from acute myeloid leukaemia patients in complete haematological remission

“…These results, together with the evidence that effective LAK cells may be generated from leukaemic patients in disease remission (Lauria et al , 1994), are in contrast to the defective killing capacity of LAK effectors generated from AML patients at diagnosis (Foa et al , 1991a). T and cytotoxic cells infiltrating or associated with solid and haematological malignancies present several functional defects in molecules involved in the triggering of effector functions (Tursz et al , 1982; Ruco et al , 1983; Frydecka, 1985; Foa et al , 1990; Nakagomi et al , 1993; Lai et al , 1996; Kono et al , 1996); these abnormalities may be secondary to the presence of the tumour (Whiteside, 1999) and are usually reversible after activation of these effectors (Rabinowich et al , 1996; Renner et al , 1996).…”

Expression of p75 chain of IL-2 receptor in the early immunological reconstitution after allogeneic bone marrow transplantation

“…Surface expression of p75 chain of 1L-2R has been correlated with the capability to mediate LAK activity [13][14][15]. LAK eells are known to be able to lyse, both in vitro and in vivo., a wide variety of target cells, including autologous malignant cells, and are believed to be potentially able to play an important role in anti-tumour immunosurveillance [33][34][35][36][37].…”