免疫检查点标记物的转录组表达谱是感兴趣的,以便破译免疫疗法应答和抗性的机制。总的来说,本研究对514例各种实体瘤患者进行了回顾性分析。肿瘤检查点标志物(ADORA2A,BTLA,CD276,CTLA4,IDO1,IDO2,LAG3,NOS2,PD-1,PD-L1,PD-L2,PVR,TIGIT,TIM3,VISTA,和VTCN)根据参考人群从0-100百分位数进行排序。每个检查点的表达与癌症类型相关,微卫星不稳定性(MSI),肿瘤突变负荷(TMB),通过免疫组织化学(IHC)和程序性死亡配体1(PD-L1)。该队列包括30种不同的肿瘤类型,结直肠癌是最常见的(27%)。当RNA百分位数排序值被归类为“低”(0-24)时,“中级”(25-74),和“高”(75-100),每位患者都有一个独特的16个检查点标记分类表达组合.观察到一些检查点标记与癌症类型之间的关联;NOS2在结直肠癌和胃癌中的表达明显更高(P<0.001)。主成分分析显示16个检查点标记的组合RNA表达模式与癌症类型之间没有明确的关联。TMB,MSI或PD-L1IHC。免疫检查点RNA表达因患者而异,在肿瘤类型内和肿瘤类型之间,尽管结直肠癌和胃癌显示出最高水平的NOS2,这是炎症和免疫抑制的介质。没有与MSI相关的特定组合表达模式,TMB或PD-L1IHC。下一代免疫疗法试验可能受益于患者肿瘤的个体分析,作为特定免疫调节方法的选择标准。
Transcriptomic expression profiles of immune checkpoint markers are of interest in order to decipher the mechanisms of immunotherapy response and resistance. Overall, 514 patients with various solid tumors were retrospectively analyzed in this study. The RNA expression levels of tumor checkpoint markers (ADORA2A, BTLA, CD276, CTLA4, IDO1, IDO2, LAG3, NOS2, PD-1, PD-L1, PD-L2, PVR, TIGIT, TIM3, VISTA, and VTCN) were ranked from 0-100 percentile based on a reference population. The expression of each checkpoint was correlated with cancer type, microsatellite instability (MSI), tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) by immunohistochemistry (IHC). The cohort included 30 different tumor types, with colorectal cancer being the most common (27%). When RNA percentile rank values were categorized as \"Low\" (0-24), \"Intermediate\" (25-74), and \"High\" (75-100), each patient had a distinctive portfolio of the categorical expression of 16 checkpoint markers. Association between some checkpoint markers and cancer types were observed; NOS2 showed significantly higher expression in colorectal and stomach cancer (P < 0.001). Principal component analysis demonstrated no clear association between combined RNA expression patterns of 16 checkpoint markers and cancer types, TMB, MSI or PD-L1 IHC. Immune checkpoint RNA expression varies from patient to patient, both within and between tumor types, though colorectal and stomach cancer showed the highest levels of NOS2, a mediator of inflammation and immunosuppression. There were no specific combined expression patterns correlated with MSI, TMB or PD-L1 IHC. Next generation immunotherapy trials may benefit from individual analysis of patient tumors as selection criteria for specific immunomodulatory approaches.