Milione Massimo, Boeri Mattia, Cantarutti Anna, Centonze Giovanni, Busico Adele, Suatoni Paola, Garzone Giovanna, Cattaneo Laura, Tamborini Elena, Perrone Federica, Mangogna Alessandro, Corrao Giovanni, Pruneri Giancarlo, Sozzi Gabriella, Anichini Andrea, Pastorino Ugo
Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133 Milan, Italy.
Tumour Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Cancers (Basel). 2020 Jul 7;12(7):1828. doi: 10.3390/cancers12071828.
Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35% of LC as well as lower HLA-I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a "low inflammatory profile" subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88% against 8% was associated with low and high-risk profiles ( < 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation.
近25%的肺癌（LC）发生在从不吸烟的人群中。基于血浆C反应蛋白水平（CRP）的LC炎症特征可独立于吸烟状态预测死亡率。我们假设：CRP可能与从不吸烟者的肿瘤免疫微环境（TIC）相关，并且这两个参数都可能改善他们的预后。选择了68例CRP高或低的从不吸烟的LC患者。在对手术样本进行TIC评估时，通过免疫组织化学评估程序性细胞死亡蛋白1（PD-1）及其配体（PD-L1）、人类白细胞抗原（HLA-DR和HLA-I）、CD8、CD4、CD3、CD33、CD163和CD68。通过分类与回归树分析生成基于TIC评分的分类模型。通过靶向二代测序评估肿瘤突变负荷。仅高CRP（H-CRP）亚组显示35%的LC中有PD-L1表达，并且其基质细胞中的HLA-I和HLA-DR较低。CD3、CD4、CD8、HLA-I、HLA-DR肿瘤细胞染色与“低炎症特征”亚组相关。CRP和LC免疫特征驱动临床结局：低风险和高风险特征的5年生存率分别为88%和8%（<0.0001）。CRP和肿瘤免疫微环境评估可能改善从不吸烟的LC患者的临床结局预测。
