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

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.

• Authors: Jie Mei, Guanyu Jiang, Yundi Chen, Yongrui Xu, Yuan Wan, Ruo Chen, Feng Liu, Wenjun Mao, Mingfeng Zheng, Junying Xu
• Journal: BMC cancer (BMC Cancer) Vol. 22 Issue 1 Pg. 738 (Jul 06 2022) ISSN: 1471-2407 [Electronic] England
• PMID: 35794593 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Biomarkers, Tumor
• HLA-DR alpha-Chains
• Immune Checkpoint Inhibitors
• Immunologic Factors
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Biomarkers, Tumor (immunology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, immunology)
• HLA-DR alpha-Chains (immunology)
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immunologic Factors
• Immunotherapy
• Lung Neoplasms (drug therapy, genetics, immunology)
• Predictive Value of Tests
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, immunology)
• Tumor Microenvironment