Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer.
Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer.
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非小细胞肺癌髓样细胞的定量组织分析及其作用。
DOI：
10.1136/jitc-2022-005025
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发表时间：
2022-07
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
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作者：
尽管先天免疫在抗肿瘤反应中的重要作用，但关于人类非小细胞肺癌（NSCLC）的髓样组成在组织学和分子亚型方面知之甚少。我们使用多重定量免疫荧光（QIF）来测量大型回顾性NSCLC收集中主要髓系细胞亚群的分布和临床意义。我们建立了一个QIF面板，以定位固定的人NSCLC中的主要髓系细胞亚群，包括所有细胞的4 '，6-二脒基-2-苯基吲哚，肿瘤上皮细胞的泛细胞角蛋白，M1样巨噬细胞的CD 68;以及CD 11b加HLA-DR，以询问成熟和未成熟的髓系细胞群，如髓系来源的抑制细胞（MDSC）。我们询问了四个基于组织微阵列的队列中的793个NSCLC：具有不同NSCLC亚型的#1（Yale，n=379）和#2（Greece，n=230）;具有分子注释的肺腺癌（ADC）的#3（Yale，n=138）;以及具有患者匹配的NSCLC和形态学正常的肺组织的#4（Yale，n=46）。我们研究了标记物水平、骨髓细胞特征、临床病理/分子变量和生存率之间的关系。与匹配的非肿瘤肺组织相比，肿瘤中CD 68 + M1样巨噬细胞的水平显著较低，CD 11b +/HLA-DR− MDSC样细胞的比例显著较高。HLA-DR在来自具有升高的CD 68表达的肿瘤的髓样细胞中始终较高。在所有队列中，鳞状细胞癌（SCC）的基质CD 11b显著高于ADC，EGFR突变的肺ADC显示出低于KRAS突变肿瘤的CD 11b水平。基质CD 68和HLA-DR表达细胞的增加与来自两个独立NSCLC队列的ADC的更好存活相关。在SCC中，间质CD 11b或HLA-DR表达增加与5年生存期缩短的趋势相关。非小细胞肺癌显示出相对于非肿瘤肺不利的髓样免疫结构，并在组织学上表现出不同的髓样细胞谱，并存在主要的致癌驱动突变。在肺ADC中，M1样基质促炎性髓样细胞升高是预后因素，但在SCC中不是。
Despite the prominent role of innate immunity in the antitumor response, little is known about the myeloid composition of human non-small cell lung cancer (NSCLC) with respect to histology and molecular subtype. We used multiplexed quantitative immunofluorescence (QIF) to measure the distribution and clinical significance of major myeloid cell subsets in large retrospective NSCLC collections. We established a QIF panel to map major myeloid cell subsets in fixed human NSCLC including 4’,6-Diamidino-2-Phenylindole for all cells, pancytokeratin for tumor-epithelial cells, CD68 for M1-like macrophages; and CD11b plus HLA-DR to interrogate mature and immature myeloid cell populations such as myeloid derived suppressor cells (MDSCs). We interrogated 793 NSCLCs represented in four tissue microarray-based cohorts: #1 (Yale, n=379) and #2 (Greece, n=230) with diverse NSCLC subtypes; #3 (Yale, n=138) with molecularly annotated lung adenocarcinomas (ADC); and #4 (Yale, n=46) with patient-matched NSCLC and morphologically-normal lung tissue. We examined associations between marker levels, myeloid cell profiles, clinicopathologic/molecular variables and survival. The levels of CD68+ M1 like macrophages were significantly lower and the fraction of CD11b+/HLA-DR− MDSC-like cells was prominently higher in tumor than in matched non-tumor lung tissues. HLA-DR was consistently higher in myeloid cells from tumors with elevated CD68 expression. Stromal CD11b was significantly higher in squamous cell carcinomas (SCC) than in ADC across the cohorts and EGFR-mutated lung ADCs displayed lower CD11b levels than KRAS-mutant tumors. Increased stromal CD68- and HLA-DR-expressing cells was associated with better survival in ADCs from two independent NSCLC cohorts. In SCC, increased stromal CD11b or HLA-DR expression was associated with a trend towards shorter 5-year survival. NSCLCs display an unfavorable myeloid immune contexture relative to non-tumor lung and exhibit distinct myeloid-cell profiles across histologies and presence of major oncogenic driver-mutations. Elevated M1-like stromal proinflammatory myeloid cells are prognostic in lung ADC, but not in SCC.
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DOI：
10.1016/j.jtho.2018.09.012
发表时间：
2018-12
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Toki MI;Mani N;Smithy JW;Liu Y;Altan M;Wasserman B;Tuktamyshov R;Schalper K;Syrigos KN;Rimm DL
通讯作者：
Rimm DL
影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
6.4
作者：
Davies LC;Taylor PR
通讯作者：
Taylor PR
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
11.2
作者：
Karakasheva TA;Waldron TJ;Eruslanov E;Kim SB;Lee JS;O'Brien S;Hicks PD;Basu D;Singhal S;Malavasi F;Rustgi AK
通讯作者：
Rustgi AK