Mucin-1-related T cell infiltration in colorectal carcinoma |
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Authors: | W M C Mulder M J Stukart E de Windt J Wagstaff R J Scheper E Bloemena |
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Institution: | (1) Department of Pathology Free University Hospital, De Boelelaan 1117, 1017 HV Amsterdam, The Netherlands Fax: +31 (0) 20 444 2964, NL;(2) Department of Oncology, Free University Hospital, Amsterdam, The Netherlands, NL |
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Abstract: | Mucins (MUC) are highly glycosylated molecules widely expressed on epithelia of different origins, including colonic mucosa.
Altered glycosylation processes in tumour cells result in the exposure of normally cryptic peptide epitopes, which may then
be recognized as tumour-specific antigens. Recently, MUC1-specific antibodies were detected in the serum of a broad range
of cancer patients, and from different tumours tumour-specific cytotoxic T lymphocytes (CTL) were isolated that recognized
MUC1. Absence of HLA restriction in the recognition has been ascribed to the highly repetitive sequence of the polypeptide
core, allowing simultaneous recognition of multiple identical epitopes and cross-linking and aggregation of T cell receptor
on mucin-specific T cells. We investigated the expression of MUC1 epitopes in 56 cell suspensions from Dukes’ B to D colorectal
carcinomas using antibodies that recognize distinct peptide sequences on the glycosylated or deglycosylated MUC1 protein backbone.
No relation was observed between MUC1 expression, or the extent of its glycosylation, and Dukes’ stage, tumour location and
tumour differentiation, but a positive correlation was detected between the percentages of tumour cells expressing mucin-1
and the numbers of CD3+ infiltrating cells. These tumour-infiltrating lymphocytes contained, however, only a few MUC1-specific T lymphocytes, as
CTL showing preferential killing of MUC1-expressing target cells were only obtained from one tumour. Since, in addition, the
majority of colorectal carcinomas were found to express the fully glycosylated MUC1 glycoprotein, its potential role as a
target antigen for T-lymphocyte-mediated immunotherapy in this tumour type is probably limited.
Received: 2 April 1996 / Accepted: 28 May 1996 |
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Keywords: | Mucin 1 T cell infiltration Colorectal carcinoma |
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