Senarathne Wijendra, Vranic Semir, Xiu Joanne, Rose Inga, Gates Peggy, Gatalica Zoran
Caris Life Sciences, Phoenix, AZ, USA.
College of Medicine, Qatar University, Doha, Qatar.
Ann Diagn Pathol. 2018 Apr;33:62-68. doi: 10.1016/j.anndiagpath.2017.12.004. Epub 2017 Dec 13.
Lungs are among the most common sites for development of both primary and metastatic carcinomas. Tumor cells expression (TC) of PD-L1 is an important predictor of the of response to immune check-point inhibition in NSCLC, while the composition of the immune cells (IC) in the tumor microenvironment including PD-L1+ cells is believed to predict responses in tumors of some other primary sites. Total mutational load (TML) and microsatellite instability (MSI) also play a role in response to the immune checkpoint blockade. We investigated immune microenvironment characteristics (PD-1, PD-L1, CD8) of 257 lung biopsies including 81 primary (NSCLC) and 176 metastatic tumors to the lungs. TML and MSI were calculated from massively parallel sequencing (592-gene panel). TC expression of PD-L1 was more common in NSCLC than in metastatic carcinomas (28% vs. 10%, p=0.009), while PD-L1-positive IC were present at relevant percentages (1-5%) exclusively in metastatic carcinomas (31% IC positive vs. 0%, p<0.001). Metastatic carcinomas carried significantly lower TML in comparison with the NSCLCs (6.6 mutations on average vs. 10, p=0.01). All primary NSCLC were microsatellite stable, and only 2 metastatic carcinomas exhibited MSI-H status. The number of PD-1+ and CD8+ tumor infiltrating lymphocytes did not differ significantly between the primary and metastatic carcinomas. Our study revealed significant differences in tumor immune microenvironment (PD-L1 in IC and TC), and its relationship to TML between NSCLC and metastatic cancers. These differences could determine the choice of a predictive biomarker test and subsequently effect(s) of the immune therapy treatments in various advanced cancers.
肺是原发性和转移性癌最常见的发生部位之一。非小细胞肺癌（NSCLC）中程序性死亡受体配体1（PD-L1）的肿瘤细胞表达（TC）是免疫检查点抑制反应的重要预测指标，而肿瘤微环境中免疫细胞（IC）的组成，包括PD-L1+细胞，被认为可预测其他一些原发部位肿瘤的反应。总突变负荷（TML）和微卫星不稳定性（MSI）在免疫检查点阻断反应中也起作用。我们研究了257例肺活检标本的免疫微环境特征（PD-1、PD-L1、CD8），其中包括81例原发性（NSCLC）和176例肺转移性肿瘤。通过大规模平行测序（592基因panel）计算TML和MSI。PD-L1的TC表达在NSCLC中比在转移性癌中更常见（28%对10%，p = 0.009），而PD-L1阳性IC仅在转移性癌中以相关百分比（1 - 5%）存在（31%的IC阳性对0%，p < 0.001）。与NSCLC相比，转移性癌的TML显著更低（平均6.6个突变对10个，p = 0.01）。所有原发性NSCLC均为微卫星稳定，只有2例转移性癌表现为高度微卫星不稳定（MSI-H）状态。原发性和转移性癌之间，PD-1+和CD8+肿瘤浸润淋巴细胞的数量没有显著差异。我们的研究揭示了NSCLC和转移性癌之间肿瘤免疫微环境（IC和TC中的PD-L1）及其与TML的关系存在显著差异。这些差异可能决定预测性生物标志物检测的选择，以及随后各种晚期癌症免疫治疗的效果。
