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

• 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: 631/250/21/324; 631/67/580; 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
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-021-01400-2

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.