Remodeling the tumor-immune microenvironment by anti-CTLA4 blockade enhanced subsequent anti-PD-1 efficacy in advanced nasopharyngeal carcinoma
Yuxiang Ma, Huaqiang Zhou, Fan Luo, Yang Zhang, Changbin Zhu, Weiwei Li, Zhan Huang, Jingbo Zhao, Jinhui Xue, Yuanyuan Zhao, Wenfeng Fang, Yunpeng Yang, Yan Huang, Li Zhang, Hongyun Zhao
Abstract
Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells.