肿瘤细胞治疗研究
英文原题：Infiltration of NK and plasma cells is associated with a distinct immune subset in non-small cell lung cancer.
基于RNA测序数据，在197例患者中建立了转录组免疫模式。
肿瘤微环境中的免疫细胞是免疫治疗的核心靶点，但其作用并不稳定。本研究的目的是表征非小细胞肺癌（NSCLC）中与分子和临床病理特征相关的新型免疫细胞浸润模式。在包含357例NSCLC病例的组织微阵列上标注了淋巴细胞（CD3+、CD4+、CD8+、CD20+、FOXP3+、CD45RO+）、巨噬细胞（CD163+）、浆细胞（CD138+）、NK细胞（NKp46+）、PD1+和PD-L1+。通过靶向测序分析了82个基因的体细胞突变，并估算了肿瘤突变负荷评分。基于RNA测序数据，在197例患者中建立了转录组免疫模式。免疫细胞浸润具有变异性，且与特定突变仅显示出较弱的关联。先前定义的免疫表型模式——荒漠型、炎症型和免疫排斥型——分别占病例的30%、13%和57%。值得注意的是，mRNA免疫激活和高估算肿瘤突变负荷仅为炎症型所独有。然而，在包含所有免疫细胞标志物的无监督聚类分析中，这些概念性模式仅被微弱地重现。相反，识别出四种免疫类别：（1）高免疫细胞浸润，（2）高免疫细胞浸润伴大量CD20+ B细胞，（3）低免疫细胞浸润，以及（4）具有浆细胞和NK细胞印记的表型。后一类别与更好的生存相关，尽管其免疫应答相关基因（如CXCL9、GZMB、INFG、CTLA4）表达较低。这种在NSCLC分子和临床背景下的区室特异性免疫细胞分析揭示了两个先前未被识别的免疫类别。在免疫治疗时代，一个精细的免疫分类，包括体液和先天免疫反应的特征，对于确定NSCLC的免疫原性效力至关重要。© 2021 作者。《病理学杂志》由 John Wiley & Sons, Ltd. 代表大不列颠及爱尔兰病理学会出版。
Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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