Immunotherapy for nasopharyngeal cancer—a review

Abstract

Nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr virus (EBV) and characterized by peritumoral immune infiltrate. Advanced NPC has high lethality. Immunotherapy directed against EBV antigen targets has been previously explored in clinical trials, and is likely to be validated as an important target in NPC as randomized data emerges in the future. Cancer vaccines and adoptive T cell therapy have been explored in the clinic, with the latter showing the greatest success. Recent advances in gene sequencing technology now allow personalized tumor epitope mapping, whilst the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis offers the opportunity to activate adaptive T cell response in vivo. Anti-PD1 antibodies have shown promising activity in early phase clinical trials, and randomized studies against chemotherapy are underway. As immunotherapy is incorporated into standard treatment paradigms, issues of optimal combinations with targeting agents, immune adjuvants, and sequence with chemotherapy and radiation therapy will need to be addressed. Effective strategies to increase tumor antigenicity, improve immunological memory and reduce immune escape, will need to be developed to improve treatment outcomes. Here we present a brief history of the evolution of immunotherapy in NPC, and highlight key concepts relevant to its further development in the clinic.

Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy

“…In those endemic areas, most NPC cases belong to the non-keratinizing subtype that is highly correlated with EBV infection, where the susceptibility to the infection is likely affected by dietary components and smoking [5]. NPC shows EBV type II pattern, where Epstein-Barr nuclear antigen 1 (EBNA1), latent membrane protein 1 (LMP1), LMP2A, LMP2B and Epstein-Barr virus-encoded small RNA (EBER) are expressed, and each of the EBV antigens contribute differentially to the development of NPC and modulation of immunosurveillance [6,7]. Of equal importance, it has been suggested that certain human leukocyte antigens (HLA), such as HLA-A*02:27 or HLA-A*11:01 increase NPC risk [8], while another report summarizes that individuals having HLA-A*02:07, HLA-A*33:03 or HLA-B*38:02 alleles result in higher risk towards NPC [7].…”

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

“…There are also ongoing clinical trials evaluating the safety and efficiency of anti-PD1 antibodies in NPC20. Clinical data have shown that the treatment response to PD-1/PD-L1 blockade was correlated with PD-1 or PD-L1 detected by immunohistochemistry (IHC)2122.…”

Partial absence of PD-1 expression by tumor-specific CD8+T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report

“…In this line, this observation strongly suggests that targeting PD-1-PD-L1 pathway by immunotherapy in LELC might not be the most appropriate strategy. Of note, relatively low rates of response to to anti-PD1 immunotherapy are being observed for NPC, which is also an EBV-related carcinoma [33] [34]. We think it is interesting that EBV-related tumors do not show high response rates to checkpoint blockade immunotherapy despite the strong T cell immunogenicity of EBV.…”