K. Chikamatsu et al., THE ROLE OF MAJOR HISTOCOMPATIBILITY COMPLEX EXPRESSION ON HEAD AND NECK-CANCER CELLS IN THE INDUCTION OF AUTOLOGOUS CYTOTOXIC T-LYMPHOCYTES, Cancer immunology and immunotherapy, 38(6), 1994, pp. 358-364
Using head and neck tumors, we studied the role of HLA class I and DR
antigens on tumor cells in cytotoxic T lymphocyte (CTL) induction. Exp
ression of major histocompatibility complex (MHC) antigens was investi
gated by two-color flow cytometry analysis and for this study we used
the tumor cells, over 50% of which expressed both HLA class I and DR a
ntigens on their surface. In seven cases, tumor cells were divided int
o three groups according to the specificity of monoclonal antibodies (
mAb) to MHC to study the role of MHC antigens on tumor cells in CTL in
duction: one was not blocked (MHC double-positive tumor), a second was
blocked by anti-class I mAb (class-I-negative DR-positive tumor) and
third was blocked by anti-DR mAb (class-I-positive DR-negative tumor).
Subsequently, these tumors were used to stimulate an autologous mixed
lymphocyte/tumor cell culture for 5 days (MLTC) followed by further c
ultivation with interleukin-2 for 12 days. The induced autologous tumo
r killer cells were most cytotoxic when non-treated tumors, which cons
ist mainly of cells that are both HLA-class I and DR-positive, were us
ed as stimulator cells. When the tumor cells blocked by anti-DR mAb we
re used as stimulators, autologous tumor killer activity was lower tha
n that induced by tumor cells blocked by anti-class-I mAb. Moreover, c
ytolysis by autologous tumor killer cells induced by stimulation of no
n-treated tumor cells was blocked during the effector phase, 26.6%-42.
3% and 32.7%-53.8% by anti-class-I and anti-DR mAb respectively, sugge
sting that majority of the autologous tumor killer cells are MHC-restr
icted CD8+ or CD4+ CTL. These results suggest that both MHC class I an
d class II antigens on head and neck tumor cells play a critical role
in inducing CTL.