M. Hirashima et al., ENHANCEMENT OF ANTITUMOR-ACTIVITY OF NATURAL-KILLER-CELLS BY BALL-1, A B-CELL LYMPHOMA LINE, Japanese journal of cancer research, 89(4), 1998, pp. 427-435
The anti-tumor activity of human peripheral blood mononuclear cells (P
BMC) against various tumor cell line cells (K562, Daudi, KMG-2, and KA
TOIII) was enhanced by coculture with irradiated BALL-1, but not with
other irradiated B cell line cells (NALM-1, Namalwa, and Daudi). PBMC
cocultured with BALL-1, however, failed to exhibit evident cytotoxicit
y against autologous concanavalin A-induced lymphoblasts. The enhancem
ent of the anti-tumor activity seemed not to be correlated with EBNA a
nd HLA-DR expression on B cell line cells. Monoclonal antibodies (mAbs
) against interleukin (IL)-2, interferon-gamma, IL-12, IL-15, tumor ne
crosis factor-a and lymphotoxin showed little or no suppression of the
anti-tumor activity of PBMC treated with irradiated BALL-1. Furthermo
re, the culture supernatants of BALL-1 failed to enhance the anti-tumo
r activity of PBMC, suggesting no involvement of soluble factors in th
e induction of the anti-tumor activity. The anti-tumor activity of PBM
C treated with BALL-1 was synergistically enhanced by an additional IL
-2 stimulation. Periodate-lysine-paraformaldehyde-fixed, but not ethan
ol-or acetone-fixed, BALL-1 could significantly enhance the anti-tumor
activity. Furthermore, BALL-1-derived membrane fraction, but not that
of Daudi, enhances the anti-tumor activity. It was thus suggested tha
t some membrane glycoproteins on the fell surface of BALL-1 play a cru
cial role in the induction of the anti-tumor activity. By analysis usi
ng mAbs against human leukocytes, we found that depletion of CD11b, CD
16, and CD56-positive cells resulted in decreased anti-tumor activity,
suggesting that the main effector cells in the BALL-1-induced anti-tu
mor activity were natural killer (NK) cells. The present results thus
raise the possibility that BALL-1, probably via membrane glycoproteins
, modulates NK cell-mediated anti-tumor activity.