HLA Ⅱ类分子 HLA-DRA 可识别免疫热肿瘤，并预测 NSCLC 患者对抗 PD-1 免疫治疗的应答反应。

HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC.

机构信息

Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No.299, Qingyang Road, Wuxi, 214023, China.

Department of Cardiothoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, No.299, Qingyang Road, Wuxi, 214023, China.

出版信息

BMC Cancer. 2022 Jul 6;22(1):738. doi: 10.1186/s12885-022-09840-6.

BACKGROUND

Immune checkpoint blockade (ICB) only works well for a certain subset of patients with non-small cell lung cancer (NSCLC). Therefore, biomarkers for patient stratification are desired, which can suggest the most beneficial treatment.

METHODS

In this study, three datasets (GSE126044, GSE135222, and GSE136961) of immunotherapy from the Gene Expression Omnibus (GEO) database were analyzed, and seven intersected candidates were extracted as potential biomarkers for ICB followed by validation with The Cancer Genome Atlas (TCGA) dataset and the in-house cohort data.

RESULTS

Among these candidates, we found that human leukocyte antigen-DR alpha (HLA-DRA) was downregulated in NSCLC tissues and both tumor and immune cells expressed HLA-DRA. In addition, HLA-DRA was associated with an inflamed tumor microenvironment (TME) and could predict the response to ICB in NSCLC. Moreover, we validated the predictive value of HLA-DRA in immunotherapy using an in-house cohort. Furthermore, HLA-DRA was related to the features of inflamed TME in not only NSCLC but also in most cancer types.

CONCLUSION

Overall, HLA-DRA could be a promising biomarker for guiding ICB in NSCLC.

背景

免疫检查点阻断（ICB）仅对非小细胞肺癌（NSCLC）的某些特定患者群体有效。因此，需要寻找患者分层的生物标志物，以提示最有效的治疗方法。

方法

本研究分析了基因表达综合数据库（GEO）中三个免疫治疗数据集（GSE126044、GSE135222 和 GSE136961），并提取了七个交叉候选物作为潜在的 ICB 生物标志物，随后通过 TCGA 数据集和内部队列数据进行验证。

结果

在这些候选物中，我们发现人类白细胞抗原-DR 阿尔法（HLA-DRA）在 NSCLC 组织中下调，肿瘤细胞和免疫细胞均表达 HLA-DRA。此外，HLA-DRA 与炎症性肿瘤微环境（TME）相关，并可预测 NSCLC 对 ICB 的反应。此外，我们使用内部队列验证了 HLA-DRA 在免疫治疗中的预测价值。此外，HLA-DRA 不仅与 NSCLC，而且与大多数癌症类型的炎症性 TME 特征有关。