Prognostic Implications of Heterogeneity in Intra-tumoral Immune Composition for Recurrence in Early Stage Lung Cancer.
Prognostic Implications of Heterogeneity in Intra-tumoral Immune Composition for Recurrence in Early Stage Lung Cancer.
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DOI：
10.3389/fimmu.2018.02298
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发表时间：
2018
影响因子：
7.3
通讯作者：
Schuchert MJ
中科院分区：
文献类型：
--
作者：
Mony JT;Schuchert MJ
背景资料：过去的研究已经确定了与非小细胞肺癌（NSCLC）不同临床结局相关的选定免疫细胞。考虑到免疫应答是异质性的，并且临床结果可能受到各种免疫细胞类型相互作用的影响，因此必须在同一组患者中评估多种肿瘤内免疫细胞类型。目的：评估不同类型的肿瘤内免疫细胞对早期肺腺癌完全手术切除后复发的单独和联合作用。研究方法：我们获得了NCBI GEO肺腺癌数据集，这是NSCLC最常见的组织学亚型，并重新分析了292例早期癌症（IA/IB）患者的基因表达数据。CIBERSORT用于从肿瘤转录组中解析22种免疫细胞类型。进行生存分析以评估与复发相关的免疫细胞类型和基因的影响。结果如下：在22种细胞类型中，肿瘤中高比例的TcB和单核细胞-巨噬细胞与复发概率显著增加相关。相反，非Treg CD 4 + T细胞和浆细胞比例增加与复发概率降低相关。CCL 20（其可指导B细胞谱系的细胞的迁移）、XCL 1（与原型Th 1应答相关）和免疫球蛋白链IGHV 4.34和IGLV 6.57的较高表达与显著较低的复发概率相关。重要的是，包含这四种细胞类型的肿瘤内免疫表型在患者中不同，并且根据阳性和阴性预后因素的净水平与复发差异相关。尽管肿瘤内浆细胞水平较高，但伴随的单核细胞-巨噬细胞水平较高使80个月时的无复发率从约80%降至约50%（p < 0.05）。此外，基于从四种细胞类型水平估计的评分对患者进行分层，能够识别术后复发概率显著增加（约50%）的患者。重要性：我们的分析表明，除了肿瘤中的T细胞和非TregCD 4 + T细胞之外，巨噬细胞和浆细胞的伴随水平可以识别具有更大复发风险的早期肺癌患者。
Background: Studies in the past have identified selected immune cells that associate with different clinical outcomes in non-small cell lung cancer (NSCLC). Considering the fact that immune responses are heterogenous and that the clinical outcome could be influenced by the interplay of various immune cell types, it is imperative to evaluate multiple intra-tumoral immune cell types in the same set of patients. Objective: To evaluate the individual and combined effects of diverse intra-tumoral immune cell types on recurrence after complete surgical resection in early stage lung adenocarcinoma. Methods: We obtained NCBI GEO datasets for lung adenocarcinoma, the most prevalent histological subtype of NSCLC and re-analyzed the gene expression data of 292 patients with early stage cancer (IA/IB). CIBERSORT was used to resolve 22 immune cell types from the tumor transcriptomes. Survival analysis was carried out to assess the effect of immune cell types and genes associated with recurrence. Results: Out of the 22 cell types, a high proportion of Tregs and monocyte-macrophages in the tumors were associated with significantly increased probability of recurrence. Conversely, increased proportion of non-Treg CD4+ T cells and plasma cells were associated with a lower probability of recurrence. The higher expression of CCL20 (which can direct the migration of cells of B cell lineage), XCL1 (associated with prototypical Th1 responses) and the immunoglobulin chains IGHV4.34 and IGLV6.57 were associated with a significantly lower probability of recurrence. Importantly, the intra-tumoral immune phenotype comprising these four cell types varied among patients and differentially associated with recurrence depending on net levels of positive and negative prognostic factors. Despite a high level of intra-tumoral plasma cells, a concomitant high level of monocyte-macrophages reduced the freedom from recurrence from ~80 to ~50% at 80 months (p < 0.05). Furthermore, stratification of the patients on the basis of a score estimated from the levels of four cell types enabled the identification of patients with significantly increased probability of recurrence (~50%) after surgery. Significance: Our analysis suggests that concomitant levels of macrophages and plasma cells, in addition to the T regs and non-TregCD4+ T cells in tumors can identify patients with early stage lung cancer at greater risk of recurrence.
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CD8+ T细胞和CD4+ T细胞的同时浸润是非小细胞肺癌中的一个有利的预后因素。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
7.4
作者：
Galon J;Fox BA;Bifulco CB;Masucci G;Rau T;Botti G;Marincola FM;Ciliberto G;Pages F;Ascierto PA;Capone M
通讯作者：
Capone M
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
20.3
作者：
Krzysiek, R;Lefevre, EA;Richard, Y
通讯作者：
Richard, Y
影响因子：
9.6
作者：
Detterbeck, Frank C.;Boffa, Daniel J.;Tanoue, Lynn T.
通讯作者：
Tanoue, Lynn T.