Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma

Abstract

Abstract. Nuclear antigen-1 (NA1) protein of Epstein-Barr virus (EBV) is expressed in EBV-infected cells in the microenvironment of cancer. Since immune cells infiltrate abundantly in nasopharyngeal carcinoma (NPC) tumor tissues, we hypothesized that the local tumor microenvironment may perform an important role in the production of antibodies directed at NA1. Furthermore, we hypothesized that anti-NA1 antibody originating in the local microenvironment could be secreted into the saliva of patients with NPC. In the present study, 20 healthy controls and 39 patients with NPC treated with intensity-modulated radiation therapy were recruited for the study. Saliva and serum samples were collected from the NPC patients, and nasopharyngeal tissue samples from the patients with NPC. The titers of anti-NA1 antibody [immunoglobulin A (IgA)] were determined by ELISA. Expression of NA1, human leukocyte antigen-antigen D related (HLA-DR), cluster of differentiation (CD)80, CD86, CD3, CD4, CD19 and IgA was detected by immunohistochemical staining on paraffin-embedded nasopharyngeal tissue sections. Anti-NA1 antibodies were detected in the serum and saliva samples of the patients with NPC. In infiltrating cells, expression of HLA-DR, CD80, CD86, CD3, CD4, CD19 and IgA was detected, indicating that dendritic cells, T lymphocytes and B lymphocytes were all present in the local tumor tissues. Furthermore, expression of EBNA1 protein was detected on the membrane of the NPC tumor cells. Therefore, the NPC tumor microenvironment has the potential to initiate a humoral response to EBNA1 by producing IgA antibodies.

Decreased oral Epstein‐Barr virus DNA loads in patients with nasopharyngeal carcinoma in Southern China: A case‐control and a family‐based study

“…Previous studies revealed aberrant levels of EBV antibodies, including potential neutralized antibody, can be detected in saliva of NPC patients while not in healthy EBV carriers . A newly published paper reported that NA1‐expressed cells, antigen presenting cells (APCs), B cells can be all detected in local tumor environment of NPC . Thus, the oral EBV loads may be influenced by both local tumor and immune microenvironment in oral cavity.…”

“…35,36 A newly published paper reported that NA1-expressed cells, antigen presenting cells (APCs), B cells can be all detected in local tumor environment of NPC. 37 Thus, the oral EBV loads may be influenced by both local tumor and immune microenvironment in oral cavity. There was no obviously association between serum EBV antibodies and oral viral loads in health controls.…”

Novel Therapies Boosting T Cell Immunity in Epstein Barr Virus-Associated Nasopharyngeal Carcinoma

“…It was also discovered that tumour-derived exosomes contribute to maintaining tumour immune tolerance by favouring regulatory T cells (Tregs) [ 67 ], among other mechanisms [ 71 ]. EBV thrives on this immunosuppressive tumour microenvironment and its key contributors are viral proteins such as EBNA1 and LMP1 [ 72 , 73 ].…”

CMV and EBV targets recognized by tumor-infiltrating B lymphocytes in pancreatic cancer and brain tumors

“…NPC, gastric carcinoma 10 , Burkitt’s lymphoma, B-cell lymphomas (Hodgkin’s and non-Hodgkin’s), B cell-associated post-transplant lymphoproliferative disorder (PTLD) 58 and several T cell-associated malignancies 59 . We are not aware of studies demonstrating EBV-specific B cells in these tumor lesions, although saliva from patients with NPC were found to contain EBNA-1-specific IgA, possibly rising from TIBs – in conjunction with detection of membrane-associated EBNA-1 expressed in NPC cells 60 . Infiltration of T-bet+ (Th1) and CD20+ (B cells) in gastric carcinoma has also been associated with survival benefit 61 , lending support to the notion that EBV-specific B cells are indeed a constitutive immune cell subset in TIL.…”