Oral squamous cell carcinoma suppressed antitumor immunity through induction of PD-Ll expression on tumor-associated macrophages
Oral squamous cell carcinoma suppressed antitumor immunity through induction of PD-Ll expression on tumor-associated macrophages
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DOI：
10.1016/j.imbio.2016.12.002
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发表时间：
2017-04-01
期刊：
影响因子：
2.8
通讯作者：
Wu, Limeng
中科院分区：
文献类型：
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作者：
Jiang, Canhua;Yuan, Fulai;Wu, Limeng
口腔鳞状细胞癌（Oral squamous cell carcinoma，OSCC）是口腔中最常见的实体肿瘤。OSCC的发展和进展与抑制性M2型肿瘤相关巨噬细胞（TAM）的存在增加有关。然而，导致M2 TAM富集的潜在机制以及TAM促进肿瘤进展的途径仍不清楚。在这项研究中，我们从II期和III期患者的原发性OSCC切除术中收集TAM和肿瘤细胞。我们表明，与肿瘤周围巨噬细胞相比，TAM呈现PD-L1表达上调和诱导T细胞凋亡的能力提高。PD-L1表达水平与T细胞凋亡水平直接相关。有趣的是，具有低初始PD-L1水平的外周血单核细胞在与来自OSCC患者的原发性肿瘤细胞孵育后上调PD-L1表达并获得诱导T细胞凋亡的能力。单核细胞的PD-L1表达依赖于白细胞介素10（IL-10），因为肿瘤-单核细胞共培养物中IL-10的阻断消除了PD-L1上调。肿瘤细胞和单核细胞中的IL-10 mRNA表达也先于单核细胞中的PD-L1 mRNA表达。此外，肿瘤微环境中的IL-10浓度与TAM上的PD-L1水平直接相关。总之，这些结果表明，口腔鳞状细胞癌可以通过调节TAM直接抑制抗肿瘤T细胞免疫。(C)2016 Elsevier GmbH. All rights reserved.
Oral squamous cell carcinoma (OSCC) is the most common solid tumor in the oral cavity. Development and progression of OSCC is associated with the elevated presence of inhibitory M2 type tumor-associated macrophages (TAMs). However, the underlying mechanism leading to the enrichment of M2 TAMs and the pathway through which TAMs foster tumor progression are still unclear. In this study, we harvested TAMs and tumor tells from primary OSCC resections of stage II and stage III patients. We showed that compared to peritumoral macrophages, TAMs presented upregulated expression of PD-Ll and elevated capacity in inducing T cell apoptosis. The level of PD-Ll expression directly correlated with the level of T cell apoptosis. Interestingly, peripheral blood monocytes with low initial PD-L1 level had upregulated PD-L1 expression and acquired the ability to induce T cell apoptosis, after incubation with primary tumor cells from OSCC patients. The PD-Ll expression by monocytes depended on interleukin 10 (IL-10), since blockade of IL-10 in the tumor-monocyte coculture abrogated PD-Ll upregulation. IL-10 mRNA expression in tumor cells and monocytes also preceded PD-Ll mRNA expression in monocytes. Furthermore, the IL-10 concentration in the tumor microenvironment directly correlated with the PD-L1 level on TAMs. Together, these results suggest that OSCC could directly suppress antitumor T cell immunity through conditioning TAMs. (C) 2016 Elsevier GmbH. All rights reserved.