CXCR5 and ICOS expression identifies a CD8 T-cell subset with TFH features in Hodgkin lymphomas
CXCR5 and ICOS expression identifies a CD8 T-cell subset with TFH features in Hodgkin lymphomas
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DOI：
10.1182/bloodadvances.2018017244
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发表时间：
2018-08-14
期刊：
影响因子：
7.5
通讯作者：
Olive, Daniel
中科院分区：
文献类型：
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作者：
Le, Kieu-Suong;Ame-Thomas, Patricia;Olive, Daniel
对经典型霍奇金淋巴瘤(CHL)微环境中T细胞亚群的较好描述将有助于免疫治疗的发展。利用多色流式细胞术，我们在43个CHL组织样本中的6个组织中鉴定了CD8 T细胞亚群(CD8(CXCR5+ICOS+))，CD8(CXCR5+ICOS+)共表达CXCR5和诱导性T细胞共刺激分子(ICOS+)。这些细胞与滤泡辅助性T细胞(T-FH)有共同的表型特征，包括CCR7低表达，B细胞淋巴瘤-6、程序性细胞死亡1、B和T淋巴细胞衰减器、CD200和OX40高表达。它们细胞毒性不足，干扰素-γ分泌水平低，与肿瘤内的CD4(+)T(FH)细胞具有共同的功能特性，如产生白细胞介素4(IL-4)、IL-21、CXCL13和维持B细胞的能力。基因图谱分析显示CD8(CXCR5+ICOS+)T细胞和CD4(+)T(FH)细胞的特征有显著的相似性。良性淋巴结炎组织(n=8)无CD8(CXCR5+ICOS+)细胞。在35例B细胞淋巴瘤组织中，滤泡性淋巴瘤13例，弥漫性大细胞淋巴瘤12例，边缘带淋巴瘤3例，套细胞淋巴瘤3例，慢性淋巴细胞白血病4例，仅1例MZL标本含有CD8(CXCR5+ICOS+)。具有CD8(CXCR5+ICOS+)细胞的淋巴瘤肿瘤具有共同的组织病理学特征，包括残留的生发中心，并含有大量激活的CD8(CXCR5-ICOS+)细胞。这些数据表明CD8 T细胞分化途径导致获得一些T-FH相似性。他们提出了一种特殊的免疫编辑过程，全球CD8激活主要在HL肿瘤中起作用，但不是唯一的。
A better characterization of T-cell subsets in the microenvironment of classical Hodgkin lymphoma (cHL) would help to develop immunotherapies. Using multicolor flow cytometry, we identified in 6 of 43 cHL tissue samples a previously unrecognized subset of CD8 T cells coexpressing CXCR5 and inducible T-cell costimulator (ICOS) molecules (CD8(CXCR5+ICOS+)). These cells shared phenotypic features with follicular helper T (T-FH) cells including low CCR7 expression together with high expression of B-cell lymphoma-6, programmed cell death 1, B and T lymphocyte attenuator, CD200, and OX40. They had deficient cytotoxicity, low interferon-y secretion, and common functional properties with intratumoral CD4(+ )T(FH) cells, such as production of interleukin-4 (IL-4), IL-21, CXCL13, and capacity to sustain B cells. Gene profiling analysis showed a significant similarity between the signatures of CD8(CXCR5+ICOS+) T cells and CD4(+) T(FH )cells. Benign lymphadenitis tissues (n = 8) were devoid of CD8(CXCR5+ICOS+) cells. Among the 35 B-cell lymphoma tissues analyzed, including follicular lymphomas (n = 13), diffuse large cell lymphomas (n = 12), marginal zone lymphomas (MZLs; n = 3), mantle cell lymphomas (n = 3), and chronic lymphocytic leukemias (n = 4), only 1 MZL sample contained CD8(CXCR5+ICOS+) cells. Lymphoma tumors with CD8(CXCR5+ICOS+) cells shared common histopathological features including residual germinal centers, and contained high amounts of activated CD8(CXCR5-ICOS+) cells. These data demonstrate a CD8 T-cell differentiation pathway leading to the acquisition of some T-FH similarities. They suggest a particular immunoediting process with global CD8 activation acting mainly, but not exclusively, in HL tumors.