High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells

Abstract

High-risk human papillomaviruses (HPVs) are responsible for a subset of head and neck squamous cell carcinomas (HNSCC). Expression of class II major histocompatibility complex (MHC-II) is associated with antigen presenting cells (APCs). During inflammation, epithelial cells can be induced to express MHC-II and function as accessory APCs. Utilizing RNA-seq data from over 500 HNSCC patients from The Cancer Genome Atlas, we determined the impact of HPV-status on the expression of MHC-II genes and related genes involved in their regulation, antigen presentation, and T-cell co-stimulation. Expression of virtually all MHC-II genes was significantly upregulated in HPV+ carcinomas compared to HPV− or normal control tissue. Similarly, genes that encode products involved in antigen presentation were also significantly upregulated in the HPV+ cohort. In addition, the expression of CIITA and RFX5—regulators of MHC-II—were significantly upregulated in HPV+ tumors. This coordinated upregulation of MHC-II genes was correlated with higher intratumoral levels of interferon-gamma in HPV+ carcinomas. Furthermore, genes that encode various co-stimulatory molecules involved in T-cell activation and survival were also significantly upregulated in HPV+ tumors. Collectively, these results suggest a previously unappreciated role for epithelial cells in antigen presentation that functionally contributes to the highly immunogenic tumor microenvironment observed in HPV+ HNSCC.

High MHC-II expression in Epstein–Barr virus-associated gastric cancers suggests that tumor cells serve an important role in antigen presentation

“…The coordinated upregulation of the components of the MHC-II antigen presentation pathway, combined with the expression of exogenous viral antigens may help explain why clinical outcomes are superior for EBVaGCs compared to most other GC subtypes. An analogous situation is likely present in the tumor microenvironment of human papillomavirus positive oropharyngeal cancers, which display similar immunological characteristics to EBVaGCs, including upregulated MHC-II pathway components, and also exhibit better patient outcomes compared to those without a viral etiology 70,71 .…”

HNSCC: Tumour Antigens and Their Targeting by Immunotherapy

“…More recently, both in infectious disease and cancer, cytotoxic CD4 + T cells have been described, which can remove cells in an MHC II restricted fashion [ 63 ]. Therefore, it seems likely that the induction of both CD8 + and CD4 + T cells will be useful also in the control of HPV pos HNSCC, which express both MHC I and MHC II [ 64 ].…”

Lung adenocarcinoma‐related TNF‐α‐dependent inflammation upregulates MHC‐II on alveolar type II cells through CXCR‐2 to contribute to Treg expansion

“…Additionally, AFG 1 enhanced human leukocyte antigen‐DR (HLA‐DR) expression on human alveolar type II (AT‐II) cells but not on the co‐stimulatory molecules CD80 or CD86. MHC‐II molecules are constitutively expressed on professional antigen presenting cells (APCs) such as dendritic cells, macrophages, and B cells 7,8 . APCs present these exogenous peptides on their cell surface in the context of major MHC‐II, to activate CD4 + helper T cells in an antigen‐specific fashion.…”