Lack of MHC class I surface expression on neoplastic cells and poor activation of the secretory pathway of cytotoxic cells in oval squamous cell carcinomas
I. Cruz et al., Lack of MHC class I surface expression on neoplastic cells and poor activation of the secretory pathway of cytotoxic cells in oval squamous cell carcinomas, BR J CANC, 81(5), 1999, pp. 881-889
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the secret
ory pathway of perforin/granzymes to kill their target cells. In contrast t
o NK cells, CTL responses are MHC class 1 restricted. In this study we anal
ysed the relative activation of CTL and NK cells in relation with MHC class
1 expression on oral squamous cell carcinomas (OSCCs). MHC class I express
ion was investigated in 47 OSCCs by immunohistochemistry using HCA2, HC10 a
nd beta 2-m antibodies. The presence of CTLs, NK cells, and its activation,
was investigated in 21 of these OSCCs using respectively, CD8, CD57 and Gr
B7 antibodies. The Q-Prodit measuring system was used for quantification of
cytotoxic cells. All OSCCs showed weak or absent staining of beta 2-m on t
he cell surface. The absence of beta 2-m was significantly associated with
absent expression of MHC class 1 heavy chain as detected by HC10 antibody (
P = 0.004). in tumour infiltrates CTLs always outnumbered NK cells, as refl
ected by the ratio CD57/CD8 being always inferior to one (mean: 0.19; SD: 0
.15). The proportion of activated cytotoxic cells as detected by granzyme B
expression was generally low (mean: 8.6%; SD 8.9). A clear correlation bet
ween MHC class I expression and the relative proportion of NK cells/CTLs wa
s not found. This study shows that the majority of OSCCs show weak or absen
t expression of MHC class 1 molecules on the cell surface, possibly due to
alterations in the normal beta 2-m pathway. The low proportion of granzyme
B-positive CTLs/NK cells indicates that the secretory pathway of cytotoxici
ty is poor in these patients. The lack of correlation between MHC class I e
xpression and CTL/NK cell activation as detected by granzyme B expression s
uggests that, next to poor antigen presentation, also local factors seem to
determine the final outcome of the cytotoxic immune response. (C) 1999 Can
cer Research Campaign.