Tertiary Lymphoid Structure-Associated B Cells Enhance CXCL13+CD103+CD8+ Tissue-Resident Memory T-Cell Response to Programmed Cell Death Protein 1 Blockade in Cancer Immunotherapy

作者：Chupeng Hu, Wenhua You, Deyuan Kong, Yedi Huang, Jinying Lu, Mengya Zhao, Yu Jin, Rui Peng, Dong Hua, Dong‐Ming Kuang, Yun Chen · 发表于：Gastroenterology · 年份：2023 · DOI：10.1053/j.gastro.2023.10.022 · 被引用次数：88 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

Background & Aims Although the presence of tertiary lymphoid structures (TLS) correlates with positive responses to immunotherapy in many solid malignancies, the mechanism by which TLS enhances antitumor immunity is not well understood. The present study aimed to investigate the underlying cross talk circuits between B cells and tissue-resident memory T (Trm) cells within the TLS and to understand their role in the context of immunotherapy. Methods Immunostaining and H&E staining of TLS and chemokine (C-X-C motif) ligand 13 (CXCL13) + cluster of differentiation (CD)103 + CD8 + Trm cells were performed on tumor sections from patients with gastric cancer (GC). The mechanism of communication between B cells and CXCL13 + CD103 + CD8 + Trm cells was determined in vitro and in vivo. The effect of CXCL13 + CD103 + CD8 + Trm cells in suppressing tumor growth was evaluated through anti–programmed cell death protein (PD)-1 therapy. Results The presence of TLS and CXCL13 + CD103 + CD8 + Trm cells in tumor tissues favored a superior response to anti–PD-1 therapy in patients with GC. Additionally, our research identified that activated B cells enhanced CXCL13 and granzyme B secretion by CD103 + CD8 + Trm cells. Mechanistically, B cells facilitated the glycolysis of CD103 + CD8 + Trm cells through the lymphotoxin-α/tumor necrosis factor receptor 2 (TNFR2) axis, and the mechanistic target of rapamycin signaling pathway played a critical role in CD103 + CD8 + Trm cells glycolysis during this...