The immunologic advantage of recurrent nasopharyngeal carcinoma from the viewpoint of Galectin-9/Tim-3-related changes in the tumour microenvironment

Tseng-Cheng Chen,Pei-Hsuan Lin,Jenq-Yuh Ko,Pei-Jen Lou,Chao-Hsien Chen,Cheng-Ping Wang,Chen-Tu Wu,Tsung-Lin Yang,Yih-Leong Chang

doi:10.1038/s41598-017-10386-y

Abstract

Given salvage treatment for recurrent nasopharyngeal carcinoma (NPC) remains a clinical dilemma, immunotherapy targeting NPC-specific immunosuppression may bring new hope. We analyzed the expression of CD8, CD4, Foxp3 and Tim-3 in lymphocytes, and of Galectin-9 in tumour cells between paired primary and recurrent NPC from 95 patients and we noted that there was significant increase in the expression of Galectin-9+ tumour cells (p < 0.001) and Foxp3+ lymphocytes (p < 0.001) but a significant decrease in the expression of CD8+ lymphocytes (p = 0.01) between paired primary and recurrent NPC. Of all patients, 53 patients (55.79%) and 57 patients (60%) had increased percentages of Galectin-9+ tumour cells and of Foxp3+ lymphocytes, respectively. Conversely, 42 patients (44.21%) had decreased percentages of CD8+ lymphocytes. The patients with high Galectin-9 expression in recurrent NPC frequently also had high Tim-3 (p = 0.04) and Foxp3 (p = 0.01), and low CD8 (p = 0.04) expression in lymphocytes. After multivariate analyses, low CD8 expression in lymphocytes was an independent risk factor for relapse-free survival (p = 0.002) and overall survival (p = 0.02). Our data suggests that recurrent NPC may had more immunologic advantage than primary NPC, especially the Galectin-9/Tim-3 pathway. The immunotherapies targeting Galectin-9/Tim-3/Foxp3 interaction may serve as a potential salvage treatment for recurrent NPC.

Highlights

In contrast to other head and neck squamous cell carcinomas, nasopharyngeal carcinoma (NPC) is characterized by its close association with Epstein-Barr virus (EBV) infection, poor differentiation of tumour cells and high susceptibility to radiotherapy and chemotherapy[1, 2]
The scientific aim of our study is to evaluate the consequential changes in tumour immunology from chemotherapy and radiotherapy of primary NPC and understand the possible clinical implication of immunotherapeutic potential for patients with recurrent NPC in the future
When we compared the expression of all immunologic markers (Fig. 1) in the tumour microenvironment between primary and recurrent NPC, we found significant differences in the mean percentages of Galectin-9+ tumour cells, Foxp3+ lymphocytes and CD8+ lymphocytes

Summary

Introduction

In contrast to other head and neck squamous cell carcinomas, nasopharyngeal carcinoma (NPC) is characterized by its close association with Epstein-Barr virus (EBV) infection, poor differentiation of tumour cells and high susceptibility to radiotherapy and chemotherapy[1, 2]. It is interesting and important to discover the changes of Galectin-9/Tim-3 pathway and generalized immunologic status (CD8+ , CD4+ and Foxp3+ lymphocytes in tumour microenvironment) between primary and recurrent NPC. We evaluated the paired immunologic expression of CD8+ lymphocytes, CD4+ lymphocytes, Foxp3+ lymphocytes, and the Galectin-9/Tim-3 pathway in the tumour microenvironment between primary and recurrent NPC from 95 patients. The question of whether immunotherapy could be the choice of salvage treatment is imperative to answer To answer this question, we analyzed the immunologic changes in the tumour microenvironment between primary and recurrent NPC. The scientific aim of our study is to evaluate the consequential changes in tumour immunology from chemotherapy and radiotherapy of primary NPC and understand the possible clinical implication of immunotherapeutic potential for patients with recurrent NPC in the future

Objectives

Results

Conclusion