Abstract
Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas (CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especially dendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide which has an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology and prognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy is found in the literature about the role of Tregs in CTCL. The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form Sezary syndrome (SS). Immunohistochemical expression of granulysin and FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MF and 6 SS). Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaque and higher in the more advanced stages of MF (p<0.001). All groups showed significant differences between each other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stage MF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lower in parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences between each other except between parapsoriasis and SS and between patch and plaque stages of MF. The present study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effect of FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.
Highlights
Primary cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of lymphoproliferative disorders characterized by monoclonal proliferation of skin-homing CD4+ve T lymphocytes. (Willemze et al, 2005) The major variant is Mycosis Fungoides (MF), which is confined to the skin and has a slowly progressing course over years to decades. (Quaglino et al, 2012) The less common Sézary syndrome (SS) carries a worse prognosis and is characterized by erythroderma, generalized lymphadenopathy, and leukemic blood involvement with Sézary cells (Wilcox, 2014).Granulysin is a cytotoxic molecule expressed, together with granzymes and perforin, in granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK)
Aim: The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form Sézary syndrome (SS)
The present study aims to investigate the expression 1-D) and was detected in the reactive mononuclear cells. of granulysin and FOXP3 in MF and its precursor lesion The mean counts for Granulysin in the different stages large plaque parapsoriasis and its leukemic form SS
Summary
Primary cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of lymphoproliferative disorders characterized by monoclonal proliferation of skin-homing CD4+ve T lymphocytes. (Willemze et al, 2005) The major variant is Mycosis Fungoides (MF), which is confined to the skin and has a slowly progressing course over years to decades. (Quaglino et al, 2012) The less common Sézary syndrome (SS) carries a worse prognosis and is characterized by erythroderma, generalized lymphadenopathy, and leukemic blood involvement with Sézary cells (Wilcox, 2014). Investigations showed that impaired expression of granulysin by NK cells correlates with progression of cancer and lower levels of granulysin expression denotes an immunosuppressive state in cancer bearing patients (Kishi et al, 2002) Subsequent studies confirmed this observation (Nagasawa et al, 2005; Saigusa et al, 2007). Different stages in MF was associated with FOXP3 expression in the of MF were included namely; patch stage (n=10), plaque malignant large cells (Hallermann et al, 2007), CTCL stage (n=30), tumor stage (n=8) and SS (n=6). Of granulysin and FOXP3 in MF and its precursor lesion The mean counts for Granulysin in the different stages large plaque parapsoriasis and its leukemic form SS.
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