| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Correspondence |
With interest we read the article by Felgar et al1 in which the authors suggest that the relatively low numbers of neoplastic cells in T-cell-rich B-cell lymphomas (TCRBCLs) as compared to diffuse large-B-cell lymphomas might be explained by an increased level of apoptosis of tumor cells. Furthermore, it was found that TCRBCLs have a relatively high percentage of nonactivated (TIA-1+, GrB-) cytotoxic C lymphocytes (CTLs), from which the authors conclude that the increased level of apoptosis in TCRBCLs may be explained in part by a relatively high percentage of CTLs.
We agree with Felgar et al that the increased level of apoptosis, combined with increased numbers of CTLs, may well reflect a partly effective immune response against the tumor cells. In a similar study on a large group of patients with Hodgkin's disease, we have previously found that the percentage of activated CTLs (TIA-1+, GrB+) varies strongly between the different types of cases. It appeared that patients with high numbers of activated CTLs (>15%) had a worse prognosis than Hodgkin's disease patients with low percentages of activated CTLs (<15%).2 A similar, even stronger effect was observed in anaplastic large cell lymphomas.3 Because the scoring method used by Felgar et al does not provide sufficient data to correlate with clinical outcome, further fine-tuning, preferably by an objective precise method of quantification, would be required. Although in our study the TIA-1+ cells also outnumbered the GrB+ cells, only the latter were related to clinical outcome, indicating that only the percentage of GrB+-activated CTLs seems important.
We could explain our data only by assuming that in cases with an apparently strong immune surveillance, only those tumor cells best equipped to resist CTL as well as therapy-mediated apoptosis will survive. Because in our experience a similar variety in the percentage of activated CTLs is observed between individual cases of diffuse large-B-cell lymphomas (unpublished data), a similar selection for apoptosis-resistant cells may appear in diffuse large-B-cell lymphomas and TCRBCLs. From this point of view, one would expect the presented TCRBCLs to have a worse prognosis, in general, than the diffuse large-B-cell lymphomas. This notion is supported by two studies cited by Felgar et al but is not confirmed by two other groups. Therefore, it would be important in both lymphoma types to correlate the exact percentage of activated CTLs with clinical outcome.
|
Vanderbilt University Medical Center Nashville, Tennessee
Authors' Reply:
We read with interest the letter by Oudejans et al and have
examined the survival data for the T-cell-rich large-B-cell lymphoma
(TCRBCL) cases presented in our previous study.1
In that
regard, we have identified seven cases (cases 6, 7, 10, 12, 13, 14, and
18 from the original study) with either diffuse or focal areas of
15% TIA-1+, Granzyme B+ small lymphocytes (activated cytotoxic T
cell (CTL) phenotype). Interestingly, when the survival data were
compared to those patients with <15% activated CTL in their tissue
biopsies (excluding one patient who died of unrelated causes), their
disease appeared to follow a more aggressive clinical course with
decreased survival (see ). The
overall survival at 5 years after diagnosis was 78 ± 14%
versus 43 ± 18% for the cases with <15%
versus those with 15% activated CTL, respectively.
However, as might be expected because of the low number of cases, this
value did not achieve statistical significance
(P = 0.097 by log-rank test). We are currently
planning to review similar data on a larger series of patients for whom
we have clinical follow-up.2
These findings support those previously reported by Oudejans et al3 and ten Berge et al4 for Hodgkin's disease and anaplastic large cell lymphomas, respectively. In addition, although previous studies have not looked specifically at activated versus nonactivated CTL, at least one study by Diaz et al5 examined non-Hodgkin's lymphomas for the number of TIA-1+ lymphocytes per unit area in B-cell non-Hodgkin's lymphomas of intermediate and high grade in comparison with low-grade lymphomas and reactive lymphoid hyperplasias.
We believe these data provide further support to the hypothesis that tumor surveillance may be active in TCRBCL, in that an increased number of CTL are present within the tumor. However, preliminary data indicate a probable worse survival in TCRBCL cases with an increased number of activated CTL and suggest that the ability of CTL to destroy tumor target cells may be impaired.
References
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
