• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

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.

DOI:10.1186/s12885-022-09840-6
PMID:35794593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9258174/
Abstract

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.

摘要

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。

结论

总体而言，HLA-DRA 可能是指导 NSCLC 免疫治疗的有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/46e2098afee1/12885_2022_9840_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/ea44dfe856f3/12885_2022_9840_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/ece5be9390cf/12885_2022_9840_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/7b871456da60/12885_2022_9840_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/2885b5a49eaa/12885_2022_9840_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/845e1eb73b8c/12885_2022_9840_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/46e2098afee1/12885_2022_9840_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/ea44dfe856f3/12885_2022_9840_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/ece5be9390cf/12885_2022_9840_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/7b871456da60/12885_2022_9840_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/2885b5a49eaa/12885_2022_9840_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/845e1eb73b8c/12885_2022_9840_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c6d/9258174/46e2098afee1/12885_2022_9840_Fig6_HTML.jpg

相似文献

1
HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC.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。
BMC Cancer. 2022 Jul 6;22(1):738. doi: 10.1186/s12885-022-09840-6.
2
A risk score combining co-expression modules related to myeloid cells and alternative splicing associates with response to PD-1/PD-L1 blockade in non-small cell lung cancer.一种结合与髓样细胞相关的共表达模块和可变剪接的风险评分与非小细胞肺癌对 PD-1/PD-L1 阻断的反应相关。
Front Immunol. 2023 Jul 10;14:1178193. doi: 10.3389/fimmu.2023.1178193. eCollection 2023.
3
PD-L1 Expression, Tumor Mutational Burden, and Cancer Gene Mutations Are Stronger Predictors of Benefit from Immune Checkpoint Blockade than HLA Class I Genotype in Non-Small Cell Lung Cancer.程序性死亡配体 1 表达、肿瘤突变负荷和癌症基因突变是预测非小细胞肺癌免疫检查点阻断获益的更强指标，优于 HLA Ⅰ类基因分型。
J Thorac Oncol. 2019 Jun;14(6):1021-1031. doi: 10.1016/j.jtho.2019.02.008. Epub 2019 Feb 16.
4
Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer.非小细胞肺癌中致癌基因特异性的肿瘤突变负担、PD-L1 表达和免疫治疗结果的差异。
J Immunother Cancer. 2021 Aug;9(8). doi: 10.1136/jitc-2021-002891.
5
Tumor mutational load, CD8 T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients.肿瘤突变负荷、CD8 T 细胞、PD-L1 表达和 HLA Ⅰ类分子表达指导 NSCLC 患者的免疫治疗决策。
Cancer Immunol Immunother. 2020 May;69(5):771-777. doi: 10.1007/s00262-020-02506-x. Epub 2020 Feb 12.
6
HLA class II immunogenic mutation burden predicts response to immune checkpoint blockade.HLA Ⅱ类免疫原性突变负担可预测免疫检查点阻断的反应。
Ann Oncol. 2022 Jul;33(7):728-738. doi: 10.1016/j.annonc.2022.03.013. Epub 2022 Mar 23.
7
Robust Prediction of Immune Checkpoint Inhibition Therapy for Non-Small Cell Lung Cancer.免疫检查点抑制剂治疗非小细胞肺癌的稳健预测。
Front Immunol. 2021 Apr 13;12:646874. doi: 10.3389/fimmu.2021.646874. eCollection 2021.
8
TCR Repertoire Diversity of Peripheral PD-1CD8 T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non-Small Cell Lung Cancer.外周 PD-1CD8 T 细胞 TCR repertoire 多样性预测非小细胞肺癌患者免疫治疗后的临床结局。
Cancer Immunol Res. 2020 Jan;8(1):146-154. doi: 10.1158/2326-6066.CIR-19-0398. Epub 2019 Nov 12.
9
Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer.用于预测非小细胞肺癌中检查点免疫疗法反应的新兴血液生物标志物
Front Immunol. 2020 Oct 16;11:603157. doi: 10.3389/fimmu.2020.603157. eCollection 2020.
10
Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non-small cell lung cancer.他汀类药物重塑炎症肿瘤微环境，并增强非小细胞肺癌的免疫检查点阻断。
JCI Insight. 2022 Sep 22;7(18):e161940. doi: 10.1172/jci.insight.161940.

引用本文的文献

1
Association of HLA-DRA expression with prognosis and tumor microenvironment in clear cell renal cell carcinoma.HLA-DRA表达与透明细胞肾细胞癌预后及肿瘤微环境的关联
Sci Rep. 2025 Aug 10;15(1):29270. doi: 10.1038/s41598-025-13665-1.
2
Neoadjuvant PD-1 blockade induces the autophagy of immune cells: a new target for synergistic therapy of recurrent glioblastoma.新辅助PD-1阻断诱导免疫细胞自噬：复发性胶质母细胞瘤协同治疗的新靶点。
Biochem Biophys Rep. 2025 Jun 27;43:102119. doi: 10.1016/j.bbrep.2025.102119. eCollection 2025 Sep.
3
Gene Methylation in Tumors with Low CD8 T-Cell Infiltration Drives Positive Prognostic Overall Survival Responses in Pancreatic Ductal Adenocarcinoma.

本文引用的文献

1
TMEM139 prevents NSCLC metastasis by inhibiting lysosomal degradation of E-cadherin.跨膜蛋白139通过抑制E-钙黏蛋白的溶酶体降解来预防非小细胞肺癌转移。
Cancer Sci. 2022 Jun;113(6):1999-2007. doi: 10.1111/cas.15341. Epub 2022 Apr 1.
2
CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy.CD74 和 HLA-DRA 在宫颈癌发生中的作用：抗肿瘤治疗的潜在靶点。
Medicina (Kaunas). 2022 Jan 26;58(2):190. doi: 10.3390/medicina58020190.
3
Cancer statistics, 2022.癌症统计数据，2022 年。
低CD8 T细胞浸润肿瘤中的基因甲基化驱动胰腺导管腺癌的总体生存预后良好。
Int J Mol Sci. 2025 Jun 10;26(12):5567. doi: 10.3390/ijms26125567.
4
Development of an immune-related gene signature applying Ridge method for improving immunotherapy responses and clinical outcomes in lung adenocarcinoma.应用岭回归方法开发免疫相关基因特征以改善肺腺癌免疫治疗反应和临床结局
PeerJ. 2025 May 8;13:e19121. doi: 10.7717/peerj.19121. eCollection 2025.
5
Imaging antigen processing and presentation in cancer.癌症中成像抗原加工与呈递
Immunother Adv. 2025 Feb 4;5(1):ltaf002. doi: 10.1093/immadv/ltaf002. eCollection 2025.
6
PD-L1 Scoring Models for Non-Small Cell Lung Cancer in China: Current Status, AI-Assisted Solutions and Future Perspectives.中国非小细胞肺癌的PD-L1评分模型：现状、人工智能辅助解决方案及未来展望
Thorac Cancer. 2025 Apr;16(7):e70042. doi: 10.1111/1759-7714.70042.
7
The Detection of Lung Cancer Cell Profiles in Mediastinal Lymph Nodes Using a Hematological Analyzer and Flow Cytometry Method.使用血液分析仪和流式细胞术检测纵隔淋巴结中的肺癌细胞特征
Cancers (Basel). 2025 Jan 27;17(3):431. doi: 10.3390/cancers17030431.
8
Causal relationship, shared genes between rheumatoid arthritis and pulp and periapical disease: evidence from GWAS and transcriptome data.类风湿关节炎与牙髓根尖周病之间的因果关系、共享基因：来自 GWAS 和转录组数据的证据。
Front Immunol. 2024 Sep 13;15:1440753. doi: 10.3389/fimmu.2024.1440753. eCollection 2024.
9
Single-cell multi-modal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma.单细胞多模态染色质图谱揭示肝癌细胞中的表观遗传调控。
Clin Transl Med. 2024 Sep;14(9):e70000. doi: 10.1002/ctm2.70000.
10
The Genetic Analysis and Clinical Therapy in Lung Cancer: Current Advances and Future Directions.肺癌的基因分析与临床治疗：当前进展与未来方向
Cancers (Basel). 2024 Aug 19;16(16):2882. doi: 10.3390/cancers16162882.
CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12.
4
Predictive Biomarkers of Immune Checkpoint Inhibitor Response in Breast Cancer: Looking beyond Tumoral PD-L1.乳腺癌中免疫检查点抑制剂反应的预测生物标志物：超越肿瘤性PD-L1
Biomedicines. 2021 Dec 8;9(12):1863. doi: 10.3390/biomedicines9121863.
5
Hypoxic Characteristic Genes Predict Response to Immunotherapy for Urothelial Carcinoma.缺氧特征基因预测尿路上皮癌免疫治疗反应
Front Cell Dev Biol. 2021 Nov 25;9:762478. doi: 10.3389/fcell.2021.762478. eCollection 2021.
6
Interferon-Induced Transmembrane Protein 3 Shapes an Inflamed Tumor Microenvironment and Identifies Immuno-Hot Tumors.干扰素诱导跨膜蛋白 3 塑造炎症肿瘤微环境并鉴定免疫热肿瘤。
Front Immunol. 2021 Aug 11;12:704965. doi: 10.3389/fimmu.2021.704965. eCollection 2021.
7
YWHAZ interacts with DAAM1 to promote cell migration in breast cancer.YWHAZ与DAAM1相互作用以促进乳腺癌细胞迁移。
Cell Death Discov. 2021 Aug 27;7(1):221. doi: 10.1038/s41420-021-00609-7.
8
Siglec15 shapes a non-inflamed tumor microenvironment and predicts the molecular subtype in bladder cancer.Siglec15 塑造非炎症性肿瘤微环境，并预测膀胱癌的分子亚型。
Theranostics. 2021 Jan 1;11(7):3089-3108. doi: 10.7150/thno.53649. eCollection 2021.
9
A comparability study of natural and deglycosylated PD-L1 levels in lung cancer: evidence from immunohistochemical analysis.肺癌中天然和去糖基化 PD-L1 水平的可比性研究：免疫组化分析的证据。
Mol Cancer. 2021 Jan 7;20(1):11. doi: 10.1186/s12943-020-01304-4.
10
The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression.MHC-II 抗原呈递机制和 B7 检查点配体的表达模式与急性髓系白血病blasts 细胞 HLA-DR 的表达相关。
Immunobiology. 2021 Jan;226(1):152049. doi: 10.1016/j.imbio.2020.152049. Epub 2020 Dec 3.