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Genetics and Genomics

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

British Journal of Cancer volume 125, pages 422–432 (2021)Cite this article

Subjects

Abstract

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.

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Fig. 1: HLA mRNA expression comparison across cancer types and HLA genes.
Fig. 2: Association between HLA gene expression and genomic features.
Fig. 3: HLA gene expression associated with prognosis.
Fig. 4: Association between meta-HLA gene expression and the tumour microenvironment.
Fig. 5: HLA Class I genes associated with response to immune checkpoint blockade.

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Acknowledgements

We would like to thank all members of the Cheng lab for their suggestions and critical feedback.

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Author notes

  1. These authors contributed equally: Evelien Schaafsma, Chloe M. Fugle

Authors and Affiliations

  1. Department of Molecular and Systems Biology, Dartmouth College, Hanover, NH, USA

    Evelien Schaafsma & Xiaofeng Wang

  2. Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA

    Evelien Schaafsma, Chloe M. Fugle & Chao Cheng

  3. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Chao Cheng

  4. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Chao Cheng

  5. The Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA

    Chao Cheng

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Contributions

C.C. conceived the project. E.S., C.M.F. and C.C. performed computational analyses. E.S., C.M.F., X.W. and C.C. wrote the paper. E.S., C.M., X.W. and C.C. interpreted the results. X.W. and C.C. supervised the project. C.C., E.S., CF. and X.W. critically reviewed the content. C.C., E.S., C.F. and X.W. read and approved the final paper.

Corresponding author

Correspondence to Chao Cheng.

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Data availability

All data utilised in this study are publicly available. See ‘Methods’ for data sources.

Competing interests

The authors declare no competing interests.

Funding information

This work is supported by the Cancer Prevention Research Institute of Texas (CPRIT) (RR180061 to C.C.), the National Cancer Institute of the National Institutes of Health (1R21CA227996 to C.C.) and the T32 training grant of the National Institutes of Health (T32 AI007363 to ES). C.C. is a CPRIT Scholar in Cancer Research.

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Schaafsma, E., Fugle, C.M., Wang, X. et al. Pan-cancer association of HLA gene expression with cancer prognosis and immunotherapy efficacy. Br J Cancer 125, 422–432 (2021). https://doi.org/10.1038/s41416-021-01400-2

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