Evelien Schaafsma1,2, Chloe M Fugle2, Xiaofeng Wang1, Chao Cheng3,4,5,6. 1. Department of Molecular and Systems Biology, Dartmouth College, Hanover, NH, USA. 2. Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. 3. Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. chao.cheng@bcm.edu. 4. Department of Medicine, Baylor College of Medicine, Houston, TX, USA. chao.cheng@bcm.edu. 5. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. chao.cheng@bcm.edu. 6. The Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA. chao.cheng@bcm.edu.
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.
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.
Authors: Nadeem Riaz; Jonathan J Havel; Vladimir Makarov; Alexis Desrichard; Walter J Urba; Jennifer S Sims; F Stephen Hodi; Salvador Martín-Algarra; Rajarsi Mandal; William H Sharfman; Shailender Bhatia; Wen-Jen Hwu; Thomas F Gajewski; Craig L Slingluff; Diego Chowell; Sviatoslav M Kendall; Han Chang; Rachna Shah; Fengshen Kuo; Luc G T Morris; John-William Sidhom; Jonathan P Schneck; Christine E Horak; Nils Weinhold; Timothy A Chan Journal: Cell Date: 2017-10-12 Impact factor: 41.582
Authors: Alexandra Snyder; Tavi Nathanson; Samuel A Funt; Arun Ahuja; Jacqueline Buros Novik; Matthew D Hellmann; Eliza Chang; Bulent Arman Aksoy; Hikmat Al-Ahmadie; Erik Yusko; Marissa Vignali; Sharon Benzeno; Mariel Boyd; Meredith Moran; Gopa Iyer; Harlan S Robins; Elaine R Mardis; Taha Merghoub; Jeff Hammerbacher; Jonathan E Rosenberg; Dean F Bajorin Journal: PLoS Med Date: 2017-05-26 Impact factor: 11.069