title: Lack of MHC class I surface expression on neoplastic cells and poor activation of the secretory pathway of cytotoxic cells in oral squamous cell carcinomas.
abstract: Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the secretory pathway of perforin/granzymes to kill their target cells. In contrast to NK cells, CTL responses are MHC class I restricted. In this study we analysed the relative activation of CTL and NK cells in relation with MHC class I expression on oral squamous cell carcinomas (OSCCs). MHC class I expression was investigated in 47 OSCCs by immunohistochemistry using HCA2, HC10 and beta2-m antibodies. The presence of CTLs, NK cells, and its activation, was investigated in 21 of these OSCCs using respectively, CD8, CD57 and GrB7 antibodies. The Q-Prodit measuring system was used for quantification of cytotoxic cells. All OSCCs showed weak or absent staining of beta2-m on the cell surface. The absence of beta2-m was significantly associated with absent expression of MHC class I heavy chain as detected by HC10 antibody (P = 0.004). In tumour infiltrates CTLs always outnumbered NK cells, as reflected 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 between MHC class I expression and the relative proportion of NK cells/CTLs was not found. This study shows that the majority of OSCCs show weak or absent expression of MHC class I molecules on the cell surface, possibly due to alterations in the normal beta2-m pathway. The low proportion of granzyme B-positive CTLs/NK cells indicates that the secretory pathway of cytotoxicity is poor in these patients. The lack of correlation between MHC class I expression and CTL/NK cell activation as detected by granzyme-B expression suggests that, next to poor antigen presentation, also local factors seem to determine the final outcome of the cytotoxic immune response.
authors.affiliation: Department of Pathology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Cruz
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: I
authors.initials: I
authors.lastname: Van der Waal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism; D005260:Female; D053804:Granzymes; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology / Q000378:metabolism; D009062:Mouth Neoplasms / Q000276:immunology* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases