Guo Jhe-Cyuan, Hsu Chia-Lang, Huang Yen-Lin, Lin Chia-Chi, Huang Ta-Chen, Wu I-Chen, Lin Chen-Yuan, Lien Ming-Yu, Kuo Hung-Yang, Cheng Ann-Lii, Hsu Chih-Hung
Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Front Oncol. 2022 Jun 29;12:879398. doi: 10.3389/fonc.2022.879398. eCollection 2022.
B cells and B cell-related gene signatures in the tumor microenvironment (TME) are associated with the efficacy of anti-programmed cell death-1 (anti-PD-1) therapy in several cancer types, but not known for esophageal squamous cell carcinoma (ESCC).
Patients with advanced ESCC receiving anti-PD-1/PD-L1-based therapy were retrospectively included. A targeted RNA profiling of 770 immune-related genes from archival ESCC tissues was performed. Differential immune-related pathways and the levels of infiltrating immune cells were estimated through Gene Set Enrichment Analysis and CIBERSORT, respectively. CD19 and CD138 expression were evaluated through immunohistochemistry (IHC). The markers evaluated were correlated with clinical benefit (CB; defined as either objective response or stable disease for ≥6 months) and survival.
A total of 64 patients were enrolled. The transcriptome analysis based on 25 patients revealed that B cell signature was significantly increased in patients with CB ( <.05) and correlated with a longer PFS ( = .032) and OS ( = .013). Multiple genes representative of B cells, B cell functions, and plasma cells were upregulated in patients with CB. On further analysis of B cell subtypes in patients with CB, increase of naïve B cells ( = .057) and plasma cells ( <.01) was found but not memory B cells ( = .27). The CD19 expression in tumor stroma, detected by IHC, was higher in patients with CB ( = .033).
B cells in the TME were associated with CB in patients with advanced ESCC receiving anti-PD-1/PD-L1-based therapy.
肿瘤微环境（TME）中的B细胞和B细胞相关基因特征与几种癌症类型中抗程序性细胞死亡1（抗PD-1）治疗的疗效相关，但在食管鳞状细胞癌（ESCC）中尚不清楚。
回顾性纳入接受基于抗PD-1/PD-L1治疗的晚期ESCC患者。对存档的ESCC组织进行了770个免疫相关基因的靶向RNA分析。分别通过基因集富集分析和CIBERSORT评估差异免疫相关途径和浸润免疫细胞水平。通过免疫组织化学（IHC）评估CD19和CD138表达。评估的标志物与临床获益（CB；定义为客观缓解或疾病稳定≥6个月）和生存相关。
共纳入64例患者。基于25例患者的转录组分析显示，CB患者的B细胞特征显著增加（P<.05），并与更长的无进展生存期（PFS，P = .032）和总生存期（OS，P = .013）相关。CB患者中代表B细胞、B细胞功能和浆细胞的多个基因上调。在进一步分析CB患者的B细胞亚型时，发现幼稚B细胞增加（P = .057）和浆细胞增加（P<.01），但记忆B细胞未增加（P = .27）。通过IHC检测，CB患者肿瘤基质中的CD19表达更高（P = .033）。
在接受基于抗PD-1/PD-L1治疗的晚期ESCC患者中，TME中的B细胞与CB相关。
