Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
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DOI：
10.1186/s40169-019-0235-8
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发表时间：
2019-06-03
影响因子：
10.6
通讯作者：
Fuchs, Tina
中科院分区：
文献类型：
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作者：
Busch, Svenja;Talamini, Marina;Fuchs, Tina
背景胶质母细胞瘤是成人最常见的恶性脑肿瘤。胶质母细胞瘤通常在诊断后12- 15个月是致命的，目前的治疗方法大多只是姑息性的。因此，迫切需要新的诊断和治疗形式。由于肿瘤相关巨噬细胞是肿瘤进展和生存的关键参与者，因此在胶质母细胞瘤患者中研究其免疫学特征具有很大的潜力。最近的证据显示，可变免疫球蛋白和TCR在单核细胞亚群、体外极化的巨噬细胞和肿瘤微环境中的巨噬细胞中表达。我们着手调查循环单核细胞和肿瘤相关的巨噬细胞从胶质母细胞瘤患者的免疫球蛋白序列，以评估其潜在的新的诊断或治疗targets.ResultsWe常规发现一致的表达免疫球蛋白在肿瘤相关的巨噬细胞（TAM）和循环单核细胞在这项研究中分析的所有胶质母细胞瘤患者。然而，与B细胞相比，循环单核细胞和TAM的免疫球蛋白库通常更受限制。此外，巨噬细胞群体中的免疫球蛋白表达与肿瘤体积呈负相关。有趣的是，体细胞突变、V链使用、CDR 3长度和所使用的重链基因在从髓细胞到B细胞的免疫球蛋白的染色体14的位点上的分布的比较揭示了几乎没有差异。在患者的B淋巴细胞的免疫球蛋白库中检测不到。此外，单核细胞的免疫球蛋白库比来自相同患者的肿瘤微环境中的巨噬细胞的库更多样化，这表明肿瘤特异性免疫应答可能有利于用作诊断或治疗靶标。
BackgroundGlioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12-15months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor-associated macrophages are key players in tumor progression and survival there is large potential in investigating their immunological characteristics in glioblastoma patients. Recent evidence shows the expression of variable immunoglobulins and TCR in subpopulations of monocytes, in vitro polarized macrophages and macrophages in the tumor microenvironment. We set out to investigate the immunoglobulin sequences of circulating monocytes and tumor-associated macrophages from glioblastoma patients to evaluate their potential as novel diagnostic or therapeutic targets.ResultsWe routinely find consistent expression of immunoglobulins in tumor-associated macrophages (TAM) and circulating monocytes from all glioblastoma patients analyzed in this study. However, the immunoglobulin repertoires of circulating monocytes and TAM are generally more restricted compared to B cells. Furthermore, the immunoglobulin expression in the macrophage populations negatively correlates with the tumor volume. Interestingly, the comparison of somatic mutations, V-chain usage, CDR3-length and the distribution of used heavy chain genes on the locus of chromosome 14 of the immunoglobulins from myeloid to B cells revealed virtually no differences.ConclusionsThe investigation of the immunoglobulin repertoires from TAM and circulating monocytes in glioblastoma-patients revealed a negative correlation to the tumor volume, which could not be detected in the immunoglobulin repertoires of the patients' B lymphocytes. Furthermore, the immunoglobulin repertoires of monocytes were more diverse than the repertoires of the macrophages in the tumor microenvironment from the same patients suggesting a tumor-specific immune response which could be advantageous for the use as diagnostic or therapeutic target.