T cell receptor-zeta and granzyme B expression in mononuclear cell infiltrates in normal colon mucosa and colon carcinoma.
BACKGROUND
Whereas the presence of a lymphoid infiltrate has been associated with a favourable prognosis in colorectal carcinoma, the proliferative and cytotoxic responses of freshly isolated tumour infiltrating lymphocytes are frequently impaired. In mice, tumour induced immune suppression has been associated with a decreased expression of the zeta-chain of the T cell receptor (TCR)-CD3 complex, and loss of mRNA for granzyme B.


OBJECTIVE
To compare the expression of TCR-zeta and granzyme B in lymphocytes infiltrating normal colonic mucosa and Duke's A and D colorectal carcinomas.


METHODS
Paraffin wax embedded normal (n = 10) and malignant colonic mucosa (seven Dukes's A, nine Dukes's D).


METHODS
Immunohistochemistry.


RESULTS
The numbers of TCR-zeta + lymphocytes decreased from normal mucosa to Dukes's D carcinomas. In contrast, granzyme B+ lymphocytes were more frequent in Dukes's A carcinomas than in normal mucosa, but disappeared from advanced stage tumours. Granzyme B expressing cells were mainly CD3- (natural killer/lymphokine activated killer cells) in normal mucosa, but CD3+ in tumours, indicating the presence of activated cytotoxic T lymphocytes. In vitro culture of tumour infiltrating lymphocytes rapidly restored the expression of both molecules.


CONCLUSIONS
The frequency of TCR-zeta + and granzyme B+ lymphocytes is decreased in advanced stage colorectal carcinomas. The restoration of expression during in vitro stimulation suggests the presence of tumour derived suppressive factors in situ.
Mulder
W M
WM
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Bloemena
E
E
Stukart
M J
MJ
Kummer
J A
JA
Wagstaff
J
J
Scheper
R J
RJ
D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism*; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*
D017252:CD3 Complex; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases