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Activated cytotoxic T cells as prognostic marker in Hodgkin's disease
JJ Oudejans, NM Jiwa, JA Kummer, GJ Ossenkoppele, P van Heerde, JW Baars, PM Kluin, JC Kluin-Nelemans, PJ van Diest, JM Middeldorp and CJ Meijer
Department of Pathology, Free University Hospital, Amsterdam, The
Netherlands.
Although the results of treatment of Hodgkin's disease (HD) have improved
considerably in the last decades, the disease remains fatal in a minority
of patients. We have recently shown that numbers of activated cytotoxic T
cells (CTLs), present in tumor biopsy specimens, differ considerably among
individual HD patients. Because CTLs are the major effector cells in
elimination of neoplastic cells, we investigated whether the number of
activated CTLs is related to the clinical outcome of the individual patient
with HD. Activated CTLs present in tumor biopsy specimens of patients with
nodular sclerosis or mixed cellularity HD were identified by
immunohistochemistry using an antibody directed against granzyme B (GrB), a
major constituent of the cytotoxic granules of activated CTLs and natural
killer cells, and an antibody directed against CD8. The presence of a high
percentage of GrB+ lymphocytes was found to be an unfavorable prognostic
marker. The large majority of GrB+ cells were also CD8+, indicating that
these cells are activated CTLs. Prognosis was found to decrease with
increasing percentages of GrB+ lymphocytes. Optimal discrimination between
patients with good and poor prognosis was obtained when the threshold was
set at 15% GrB+ cells; 6 of 10 patients with > or = 15% GrB+ lymphocytes
died as a result of the disease, as compared with 6 of 70 patients with
less than 15% GrB+ lymphocytes (P < .0001). In stage-2 patients, the
percentage of GrB+ lymphocytes retained its predictive value in a
multivariate analysis including histology, sex, age, erythrocyte
sedimentation rate, and the presence of B symptoms as covariables. In
addition, patients with > or = 15% GrB+ lymphocytes had a shortened
progression-free survival time (P = .002). We conclude that a high
percentage of activated CTLs present in biopsy material of HD patients is a
strong indicator for an unfavorable clinical outcome.
Volume 89,
Issue 4,
pp. 1376-1382,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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