Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy

Background The function of major histocompatibility complex (MHC) molecules is to bind peptide fragments derived from genomic mutations or pathogens and display them on the cell surface for recognition by cognate T cells to initiate an immune response. Methods In this study, we provide a comprehensi...

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Bibliographic Details
Published in:British journal of cancer 2021-08, Vol.125 (3), p.422-432
Main Authors: Schaafsma, Evelien, Fugle, Chloe M., Wang, Xiaofeng, Cheng, Chao
Format: Article
Language:English
Subjects:
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Biomedical and Life Sciences
Biomedicine
Cancer
Cancer Research
CD4 antigen
CD4-Positive T-Lymphocytes - metabolism
Cell surface
Drug Resistance
Epidemiology
Female
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation, Neoplastic
Genomics
Histocompatibility antigen HLA
Histocompatibility Antigens Class I - genetics
Humans
Immune checkpoint
Immunotherapy
Immunotherapy - methods
Lymphocytes T
Major histocompatibility complex
Male
Medical prognosis
Metastases
Molecular Medicine
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - immunology
Neutrophil Infiltration
Oncology
Patients
Prognosis
Sequence Analysis, RNA
Survival Analysis
Treatment Outcome
Tumors
Up-Regulation
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Summary:Background The function of major histocompatibility complex (MHC) molecules is to bind peptide fragments derived from genomic mutations or pathogens and display them on the cell surface for recognition by cognate T cells to initiate an immune response. Methods In this study, we provide a comprehensive investigation of HLA gene expression in a pan-cancer manner involving 33 cancer types. We utilised gene expression data from several databases and immune checkpoint blockade-treated patient cohorts. Results We show that MHC expression varies strongly among cancer types and is associated with several genomic and immunological features. While immune cell infiltration was generally higher in tumours with higher HLA gene expression, CD4+ T cells showed significantly different correlations among cancer types, separating them into two clusters. Furthermore, we show that increased HLA gene expression is associated with prolonged survival in the majority of cancer types. Lastly, HLA gene expression is associated with patient response to immune checkpoint blockade, which is especially prominent for HLA class II expression in tumour biopsies taken during treatment. Conclusion We show that HLA gene expression is an important feature of tumour biology that has significant impact on patient prognosis.
ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-021-01400-2