Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma

Corey Smith,Margaret Mcgrath,Pauline Crooks,Sandro Porceddu,Katherine K Matthews,Laetitia Le Texier,Benedict Panizza,Michelle A Neller,Rajiv Khanna

doi:10.1038/s41698-021-00162-7

Abstract

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock for the successful implementation of ACT in clinical settings. Expression of checkpoint molecules by malignant cells can inhibit the effector function of adoptively transferred EBV-specific T cells. Here we present a novel case report of a patient with metastatic NPC who was successfully treated with a combination of EBV-specific ACT and programmed cell death-1 blockade therapy. Following combination immunotherapy, the patient showed complete resolution of metastatic disease with no evidence of disease relapse for 22 months. Follow-up immunological analysis revealed dramatic restructuring of the global T-cell repertoire that was coincident with the clinical response. This case report provides an important platform for translating these findings to a larger cohort of NPC patients.

Highlights

Nasopharyngeal carcinoma (NPC) remains a significant burden in regions of South-East Asia, with incidences as high as 20 per 100,000 in regions of Southern China[1]
The observations in the current case report demonstrate the potential impact the combination of Epstein–Barr virus (EBV)-specific Adoptive T-cell therapy (ACT) followed by checkpoint blockade treatment could have upon patients with advanced EBV-associated malignancies
What remains unclear from the current analysis is the impact of each immunotherapy approach npj Precision Oncology (2021) 24 on outcome

Summary

Introduction

Nasopharyngeal carcinoma (NPC) remains a significant burden in regions of South-East Asia, with incidences as high as 20 per 100,000 in regions of Southern China[1]. While modern radiotherapy and concurrent platinum-based chemotherapy offer high locoregional control rates, ranging between 60% and 80% for locally advanced disease, outcomes for recurrent and distant metastatic disease is poor, with 5-year survival rates less than 50%3. Recent studies using checkpoint inhibitors have demonstrated some efficacy as monotherapy in patients with recurrent or metastatic NPC, with overall response rates of 20–34% and evidence of enhanced efficacy in combination with chemotherapy[4,5,6,7]. Endemic NPC is universally associated with the presence of Epstein–Barr virus (EBV)[8,9], which establishes a latency program within the malignant cells that is characterized by a restricted gene expression profile[10]. EBV likely contributes to the oncogenic potential of NPC cells[11]

Methods

Results

Conclusion