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

Citation
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
Citations number
31
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
00070920 → ACNP
Volume
81
Issue
5
Year of publication
1999
Pages
881 - 889
Database
ISI
SICI code
0007-0920(199911)81:5<881:LOMCIS>2.0.ZU;2-F
Abstract
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.