Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival.
Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival.
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DOI：
10.18632/oncotarget.20238
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发表时间：
2017-09-19
期刊：
影响因子：
--
通讯作者：
Fichtner-Feigl S
中科院分区：
文献类型：
--
作者：
Brunner SM;Itzel T;Rubner C;Kesselring R;Griesshammer E;Evert M;Teufel A;Schlitt HJ;Fichtner-Feigl S
HCC 的免疫微环境影响患者的预后，但 B 细胞的作用仍不清楚。本研究调查了 HCC 队列中局部 B 细胞浸润对患者生存以及免疫和分子肿瘤微环境的影响。对完整癌症转录组 (N=2158) 的无监督基因表达分析揭示了 HCC 中高度共同调节的免疫簇，主要包含免疫球蛋白片段。更具体地说，在一个独立的患者队列 (N=242) 中，将 HCC 与非肿瘤性肝组织进行比较，这些 B 细胞相关基因的高表达与更好的患者预后相关 (P=0.0149)。最后，对另一个独立的切除 HCC 队列 (N=119) 进行的免疫组织化学分析表明，浸润边缘的 CD20+ 细胞 (P=0.004) 和 CD79a+ 细胞 (P=0.038) 对 HCC 的浸润与延长患者生存期相关。此外，在基因表达分析中鉴定出的免疫球蛋白片段在 B 细胞密集浸润的患者中检测到高水平。使用微阵列比较 2 个独立 HCC 组织数据库的基因表达。此外，对切除的 HCC 组织进行 CD20、CD79a 和免疫球蛋白染色，并分别分析肿瘤、浸润边缘和远处肝基质的各自细胞数。这些发现与临床数据和患者结果相关。 B 细胞浸润 HCC 与延长患者生存期相关。此外，还发现了 HCC 的独特 B 细胞样免疫球蛋白特征，这与更好的患者治疗结果相伴。我们认为，B 细胞通过分泌增加水平的具有抗肿瘤活性的免疫球蛋白来促进局部肿瘤控制。
The immunological microenvironment of HCC influences patient outcome, however, the role of B cells remains unclear. This study investigated effects of local B-cell infiltration in HCC cohorts on patient survival and immunological and molecular tumor microenvironment. Unsupervised gene expression analysis of full cancer transcriptomes (N=2158) revealed a highly co-regulated immunological cluster in HCC that mainly contained immunoglobulin fragments. More specifically, in an independent patient cohort (N=242) that compares HCC with non tumorous liver tissue high expression of these B-cell associated genes was associated with better patient outcome (P=0.0149). Conclusively, the immunohistochemical analysis of another independent cohort of resected HCCs (N=119) demonstrated that infiltration of HCCs by CD20+ cells (P=0.004) and CD79a+ cells (P=0.038) at the infiltrative margin were associated with prolonged patient survival. Further, the immunoglobulin fragments that were identified in the gene expression analysis were detected at high levels in patients with dense B-cell infiltration. Gene expression of 2 independent HCC tissue databases was compared using microarrays. Additionally, tissue of resected HCCs was stained for CD20, CD79a and immunoglobulins and analysed for the respective cell numbers separately for tumor, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome. Infiltration of HCCs by B cells is associated with prolonged patient survival. Further, a distinct B-cell like immunoglobulin profile of HCCs was identified that goes along with better patient outcome. We suggest that B cells contribute to local tumor control by secreting increased levels of immunoglobulins with antitumor activity.
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