Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma

Abstract

Peripheral blood cells from 28 patients with leukemic cutaneous T-cell lymphoma including 25 patients with Sézary syndrome were evaluated for expression of regulatory T-cell-associated markers (FoxP3, CD25, CTLA-4, neurophilin-1), T-cell activation markers (CD28 and its ligands B7.1 and B7.2) and NK cell-associated markers (NKG2D and its ligands MicA and Mic-B) using real-time quantitative polymerase chain reaction. T-plastin served as a positive genetic marker, and its expression correlated to blood tumor burden. More than 90% of samples had transcripts for CD28 and Mic-B, but less than 30% of samples expressed FoxP3, CTLA-4 and CD25. Expression of Mic-B by neoplastic cells could provide another mechanism to inhibit anti-tumor immune responses. FoxP3 expression correlated with a poor prognosis. Although the underlying mechanisms accounting for this correlation remain unclear, the expression of the Foxp3 and CTLA-4 regulatory elements indicates that a subset of leukemic cases displays a regulatory T-cell phenotype.

Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma

“…2,[19][20][21][22][23]32 In accordance with previous studies, we found no significant expression of T-plastin transcript in the 78 healthy volunteers tested, in contrast to the recent data published by Oprea et al, where 5% of healthy donors expressed a T-plastin transcript in PBLs. 33 Several reports have previously claimed that T-plastin can serve as a positive genetic marker, and that its expression correlated to blood tumor burden.…”

“…33 Several reports have previously claimed that T-plastin can serve as a positive genetic marker, and that its expression correlated to blood tumor burden. 22 However, our data showed a wide range of T-plastin expression levels among CTCL cases and 1/4 patients did not present T-plastin transcript although they exhibited clinical characteristic of a well-characterized SS.…”

“…This first set of results confirmed previously published data showing that T-plastin transcriptional expression is specific and restricted to tumor lymphocytes from patients with SS. 2,[19][20][21][22][23]32 Calcium induces T-plastin synthesis and calcineurin/NFAT pathway is involved in T-plastin regulation Cutaneous T-cell lymphomas are characterized by infiltration of activated T lymphocytes in the skin. Our present data and literature indicate that T-plastin is a specific marker of tumor T lymphocytes but this is true only for 3/4 patients with SS.…”

“…30 Moreover, T-plastin expression has been reported as increased in tumor cells that were resistant to cisplatin and reducing its expression correlated with increased cell sensitivity to cisplatin. 31 T-plastin gene expression is up-regulated in CTCL cells from SS patients and it is usually not expressed in normal T lymphocytes, 2,[19][20][21][22][23]32 except in a recent study that observed T-plastin transcription in PBLs from less than 5% healthy individuals. 33 However, the full biologic and clinical value of such aberrant T-plastin mRNA and protein expression in Sezary malignant cells remains to be clearly defined.…”

“…2,[19][20][21][22][23] T-plastin is 1 of 3 isoforms of the widely conserved actinbundling protein plastin (also called fimbrin) found in humans. 24,25 Proteins of this family share the presence of an actin-binding domain called "ABD" (30 kDa) composed of 2 calponin-homology (CH) domains.…”