Details

Autor(en) / Beteiligte

• Lv, Jiawei
• Wei, Yuan
• Yin, Jian-Hua
• Chen, Yu-Pei
• Zhou, Guan-Qun
• Wei, Chen
• Liang, Xiao-Yu
• Zhang, Yuan
• Zhang, Cui-Juan
• He, Shi-Wei
• He, Qing-Mei
• Huang, Zhuo-Li
• Guan, Jia-Li
• Shen, Jia-Yi
• Li, Xiao-Min
• Li, Jun-Yan
• Li, Wen-Fei
• Tang, Ling-Long
• Mao, Yan-Ping
• Guo, Rui
• Sun, Rui
• Zheng, Yu-Hui
• Zhou, Wen-Wen
• Xiong, Ke-Xu
• Wang, Si-Qi
• Jin, Xin
• Liu, Na
• Li, Gui-Bo
• Kuang, Dong-Ming
• Sun, Ying
• Ma, Jun

Titel

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment

Ist Teil von

• Nature medicine, 2023-06, Vol.29 (6), p.1424-1436

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.