免疫肿瘤学通路的基因表达谱（GEP）作为晚期非小细胞肺癌（NSCLC）中检查点抑制剂反应的预测指标

Gene expression profiles (GEPs) of immuno-oncologic pathways as predictors of response to checkpoint inhibitors in advanced NSCLC.

作者信息

De Marchi Pedro, Leal Leticia Ferro, da Silva Luciane Sussuchi, Cavagna Rodrigo de Oliveira, da Silva Flavio Augusto Ferreira, da Silva Vinicius Duval, da Silva Eduardo Ca, Saito Augusto O, de Lima Vladmir C Cordeiro, Reis Rui Manuel

机构信息

Oncoclinicas, Rio De Janeiro, Brazil; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP, Brazil.

出版信息

Transl Oncol. 2024 Jan;39:101818. doi: 10.1016/j.tranon.2023.101818. Epub 2023 Oct 31.

BACKGROUND

Immune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients' selection for this therapy is needed. Gene expression profile (GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario.

METHODS

Retrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes.

RESULTS

The median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ.

CONCLUSIONS

The TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

背景

免疫检查点抑制剂（ICI）彻底改变了非小细胞肺癌（NSCLC）的治疗方式。然而，需要改进该疗法的患者选择。基因表达谱（GEP）是一种很有前景的生物标志物工具。我们在NSCLC真实世界场景中评估了48种肿瘤免疫GEP的预测价值。

方法

对接受过任何线ICI治疗的巴西NSCLC患者进行回顾性队列研究。使用包含770个癌症免疫基因的nCounter泛癌IO360检测板在福尔马林固定石蜡包埋（FFPE）肿瘤组织中评估GEP。

结果

135例患者的中位年龄为61岁，大多数为男性（57.8%），有吸烟史（83.6%），东部肿瘤协作组体能状态（ECOG-PS）为0-1（88.7%），临床分期为IV期（91.9%），腺癌（65.1%）。40%的病例为一线ICI治疗，单独或联合化疗。中位随访时间为28个月，开始免疫治疗后的总生存期（免疫治疗后生存期-PIS）为17.8个月，真实世界无进展生存期为5.5个月。66例患者可行GEP分析。我们发现14种不同的GEP与PIS相关，即吲哚胺2,3-双加氧酶1（IDO1）、程序性死亡配体2（PD-L2）、细胞毒性、细胞毒性细胞、干扰素下游、细胞毒性T淋巴细胞相关蛋白4（CTLA4）、程序性死亡配体1（PD-L1）、T细胞免疫球蛋白和粘蛋白结构域蛋白3（TIGIT）、淋巴细胞、免疫蛋白酶体、耗竭性CD8、干扰素γ（IFN-γ）、肿瘤炎症特征（TIS）和抗原加工与呈递（APM）。TIS和IFN-γ是与良好预后相关的最显著GEP。TIS高表达患者的中位PIS为29.2个月，而低表达患者为15.5个月（风险比0.42；95%置信区间；0.17-0.67；p<0.05）。IFN-γ也观察到类似结果。