Blood, 1 May 2003, Vol. 101, No. 9, pp. 3342-3342
Granzyme M, a profiler of innate immune lymphocytes?
There is currently a major effort underway to identify the
protein expression patterns (proteome) of various tumor cells. Indeed,
characteristic patterns of protein expression may help determine the
specific cellular origin of the malignant cell. In this issue, Krenacs
and colleagues (page 3590) studied granzyme M (GM) expression
in various lymphomas. The granzymes (or granule enzymes) are a family
of related serine proteases that have a restricted expression within
cells of the lymphoid system. These enzymes are expressed in natural
killer (NK) cells and in T cells (predominantly CD8+
"cytotoxic" T cells) following activation (Smyth et al, J Leuk Biol. 2001;70:18-29). The granzymes are absent from macrophages, neutrophils, and B cells.
The expression of GM seems even more restricted than other granzymes.
GM is present in normal blood in rare lymphocytes such as NK cells,
/
T cells, and CD3+ CD56+ T cells, yet
is absent from T cells of the adaptive immune system even following
activation (Sayers et al, J Immunol. 2001;166:765-771). Krenacs et
al found expression of GM in 100% of NK/T lymphomas and / T-cell
lymphomas and in 85% of intestinal T-cell lymphomas. Intestinal 
CD8+ intraepithelial lymphocytes also expressed GM, leading
to the provocative suggestion that these cells may really be components of the innate immune system (despite their rearrangement of the
T-cell receptor).
GM expression was therefore maintained after tumorigenesis, and in some
situations this could have practical utility. The authors noted that
discrimination between some intestinal T-cell lymphomas (ITCLs) and
systemic anaplastic large cell lymphomas (S-ALCLs) is sometimes
difficult, yet in contrast to ITCLs, S-ALCLs rarely express GM. This
distinction would have clinical implications, since ITCL has a much
poorer prognosis than S-ALCL. Therefore, as demonstrated in this study,
GM does seem to be a useful additional marker for a further
subclassification of lymphomas. But the biologic function(s) that this
unusual enzyme performs during an innate immune response remains
mysterious and worthy of further investigation.
Thomas Sayers
National Cancer
Institute
