Lymphocytes were isolated from breast seroma fluids and used to study
the mechanism of activation of cytotoxic lymphocytes and possible role
of immunological potentiation following surgery in breast cancer pati
ents. Single or serial samples were obtained from patients who had und
ergone mastectomy or lumpectomy with axillary node dissection. Lymphoc
ytes were activated with rIL-2 (interleukin-2) and their cytotoxic act
ivity was studied against Daudi and K562 cells and against a breast tu
mor line (SKBr-3). All of the patients (21/21) responded to IL-2 stimu
lation by significant activation of cytotoxic activity. The unstimulat
ed cytotoxic activity of these cells against NK targets was low with l
ess than 10% specific release in cytotoxicity assays. In simultaneous
experiments, autologous seroma fluid was included during activation of
lymphocytes to study possible regulatory molecules that may be presen
t. In 17/21 patients, the presence of their seroma fluid, during the a
ctivation period, enhanced or did not effect the cytotoxic potential o
f their lymphocytes; inhibition was observed when seroma fluids from 4
/21 patients were included. Analysis of the cytotoxic population deriv
ed from combined IL-2 and seroma treatments indicates the presence of
cells with increased expression of CD56, and CD2, as well as in some c
ases CD16 expression. Cytotoxic lymphocytes derived from IL-2 and sero
ma treatments appeared to be more effective killers. Modulation of CD2
expression with seroma alone appeared to result in the generation of
this highly cytotoxic population. This study demonstrates the role of
CD2 expression in the effectiveness of LAK cell killing and also poten
tial benefit of an immunotherapeutic approach to the postoperative tre
atment of carcinoma of the breast. (C) 1996 Academic Press, Inc.