演題詳細

シンポジウム / Symposium

【E】シンポジウム3 (Symposium 3) : New Trends and Challenges in the Management of Malignant Lymphoma
(共催:日本リンパ網内系学会 / The Japanese Society for Lymphoreticular Tissue Research)

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日程
2013年10月11日(金)
時間
13:55 - 16:25
会場
第2会場 / Room No.2 (さっぽろ芸文館 3F 瑞雪)
座長・司会
木下 朝博 (Tomohiro Kinoshita):1、吉野 正 (Tadashi Yoshino):2
1:Aichi Cancer Center Hospital, Japan、2:Department of Pathology, Okayama University, Japan
 
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Peripheral T/NK cell lymphoma-current understanding and future perspectives

演題番号 : SY3-2

大島 孝一 (Koichi Ohshima):1

1:Department of Pathology, School of Medicine, Kurume University, Japan

 

 Peripheral T/NK cell lymphoma (PTCL) is heterogeneous in clinical features, and T-cell subtypes. We report the current understanding in PTCL.
 Chemokines are members of a family of small secreted proteins and some chemokines have received considerable attention because they display selectivity of cell targets and receptors, and are closely associated with T-cell subgroups. For example, TARC is known to bind to the CCR4 receptor, which is expressed on activated Th2 lymphocytes. CCR5 is expressed on Thl lymphocytes. To clarify the T-cell subtype in PTCL, we conducted DNA chips of chemokine, its receptor (R) and cytokines. In addition, immunological stainings were performed. In DNA chip, AITL, ALCL, NKL and ATLL showed a tendency for respective clusters, otherwise, PTCL-U clustered with AILD, ALCL and ATLL. From the gene expression profiling, CCR4, CCR3, MIG, CXCR3 and BLC were selected for immunohistochemistry. ATLL expressed CCR4. ALCL expressed CCR3, NKL expressed MIG, and AITL expressed CXCR3 and/or CXCL13. From the expression patterns, PTCL-NOS (n=134) were classified into three groups; CCR4 type (CCR4+ n=42), CCR3 type (CCR3+, n=31) and CXCR3 type (CXCR3+, n=54). The prognosis was poor for ATLL, intermediate for AITL and favorable for ALCL (P=0.0014). Among PTCL-NOS, CCR4 type, CXCR3 type and CCR3 type had prognoses equivalent to ATLL, AILD and ALCL, respectively (P<0.0001). In addition, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody was reported to be effective for the patients with CCR4 positive ATLL or PTCL-NOS.
 Recently naïve T cells are considered to develop to Th1, Th2, Th17, Treg (regulatory), and Thf (follicular). And the key molecules are considered to be respectively T-bet, GATA3, RORγt, FoxP3 and Bcl6. We stained them and tried to classify PTCL-NOS.
 Microenvironment is important to know the clinicopathological features in PTCL. AILT shows variable biological and clinical presentations. Previously we reported that the survival rate did not correlate with either T-cell clonality, presence of EBV-infected cells, or EBV-DNA copy number. In addition, there is no relationship between survival and IgH rearrangements. However, tumor-associated macrophage (TAM)/M2 macrophages significantly correlated with worse overall survival.
 ATLL express CCR4, and FoxP3 of the regulatory T-cell marker. HTLV-1 is causally linked to ATLL, but infection alone is not sufficient to result in neoplastic transformation. The p40tax viral protein leads to transcriptional activation of many genes. In addition, the HTLV-1 basic leucine zipper factor (HBZ) is thought to be important for T-cell proliferation and oncogenesis. Half of ATLL cases retain the ability to express HTLV-1 Tax which is a target of HTLV-1-specific cytotoxic T lymphocyte(CTL). An increased level of HTLV-1-specific CTL responses is observed in some asymptomatic HTLV-1 carriers. Although HTLV-1-specific CTLs are also present in peripheral blood of ATLL patients, they do not expand sufficiently. We evaluated the clinicopathological features and analyzed the staining of Tax-specific CTL and FOXP3. There were inverse correlation between Tax-specific CTL and FOXP3. In addition, the increased percentage of CD163+ TAMs were associated with worse clinical prognosis, and ATLL cell lines are significantly proliferated by direct co-culture with M2 macrophages.

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