Immune evasion of mantle cell lymphoma: expression of B7-H1 leads to inhibited T-cell response to and killing of tumor cells
Immune evasion of mantle cell lymphoma: expression of B7-H1 leads to inhibited T-cell response to and killing of tumor cells
复制标题
套细胞淋巴瘤的免疫逃避：B7-H1的表达导致T细胞对肿瘤细胞的反应受到抑制并杀死肿瘤细胞
DOI：
10.3324/haematol.2012.071340
复制
发表时间：
2013-09-01
期刊：
影响因子：
10.1
通讯作者：
Cai, Zhen
中科院分区：
文献类型：
--
作者：
Wang, Lijuan;Qian, Jianfei;Cai, Zhen
套细胞淋巴瘤免疫治疗的临床试验尚未取得令人满意的结果，部分原因是肿瘤及其微环境的抑制机制。在这里，我们研究了B7-H1，共刺激/共抑制配体B7家族的成员，在套细胞淋巴瘤介导的免疫抑制中的作用。纯化同种异体CD3+、CD4+和CD8+T细胞，并与照射后的套细胞淋巴瘤细胞共培养。从人类白细胞抗原-A*0201+健康献血者身上经体外再刺激后获得套细胞淋巴瘤反应性T细胞株，并进行功能测试。我们发现，表达在套细胞淋巴瘤细胞上的B7-H1能够抑制肿瘤细胞诱导的T细胞增殖，损害抗原特异性T细胞反应的产生，并使套细胞淋巴瘤细胞对T细胞介导的细胞溶解产生抵抗。阻断或击倒套细胞淋巴瘤细胞上的B7-H1可增强T细胞反应，恢复肿瘤细胞对T细胞介导的体外和体内杀伤的敏感性。敲除套细胞淋巴瘤细胞上的B7-H1可激活更多的CD4+或CD8+记忆效应T细胞。我们的研究首次证明，淋巴瘤细胞表达的B7-H1可能导致套细胞淋巴瘤宿主抗肿瘤免疫反应的抑制，靶向肿瘤细胞B7-H1可能是提高套细胞淋巴瘤患者免疫治疗效果的一种新途径。
Clinical trials of immunotherapy in mantle cell lymphoma have not yet delivered desirable results, partly because of the inhibitory machinery of the tumor and its microenvironment. Here we investigated the role of B7-H1, a member of the B7 family of co-stimulatory/co-inhibitory ligands, in mantle cell lymphoma-mediated immunosuppression. Allogeneic CD3+, CD4+ and CD8+ T cells were purified and co-cultured with irradiated mantle cell lymphoma cells. Mantle cell lymphoma-reactive T-cell lines from HLA-A*0201+ healthy blood donors were generated after in vitro restimulation, and were subjected to functional tests. We found that B7-H1 expressed on mantle cell lymphoma cells was able to inhibit T-cell proliferation induced by the tumor cells, impair the generation of antigen-specific T-cell responses, and render mantle cell lymphoma cells resistant to T-cell-mediated cytolysis. Blocking or knocking down B7-H1 on mantle cell lymphoma cells enhanced T-cell responses and restored tumor-cell sensitivity to T-cell-mediated killing in vitro and in vivo. Knocking down B7-H1 on mantle cell lymphoma cells primed more CD4+ or CD8+ memory effector T cells. Our study demonstrates for the first time that lymphoma cell-expressed B7-H1 may lead to the suppression of host anti-tumor immune responses in mantle cell lymphoma and targeting tumor cell B7-H1 may represent a novel approach to improve the efficacy of immunotherapy in patients with mantle cell lymphoma.