Tertiary lymphoid structures predict the prognosis and immunotherapy response of cholangiocarcinoma

作者：Taiyu Shang, Tianyi Jiang, Tao Lü, Hui Wang, Hui Wang, Xiaowen Cui, Yufei Pan, Mengyou Xu, Mengmiao Pei, Zhiwen Ding, Xiaofan Feng, Yun‐Kai Lin, Xin Li, Yexiong Tan, Feiling Feng, Hui Dong, Hongyang Wang, Hongyang Wang, Liwei Dong · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1166497 · 被引用次数：76 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer Immunotherapy and Biomarkers、Liver Diseases and Immunity

Introduction: Cholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium with a poor prognosis. The lack of biomarkers to predict therapeutic response and prognosis is one of the major challenges for CCA treatment. Tertiary lymphoid structures (TLS) provide a local and pivotal microenvironment for tumor immune responses. The prognostic value and clinical relevance of TLS in CCA remain unclear. We aimed to explore the characteristics and clinical significance of TLS in CCA. Methods: We investigated the prognostic value and clinical relevance of TLS in CCA using a surgery cohort containing 471 CCA patients (cohort 1) and an immunotherapy cohort containing 100 CCA patients (cohort 2). Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to evaluate the maturity of TLS. Multiplex IHC (mIHC) was employed to characterize the composition of TLS. Results: Different maturity of TLS were observed in CCA tissue sections. Strong staining of the four-gene signature including PAX5, TCL1A, TNFRSF13C, and CD79A were found in TLS regions. A high density of intra-tumoral TLS (T-score high) were significantly correlated with longer overall survival (OS) both in CCA cohort 1 (p = 0.002) and cohort 2 (p = 0.01), whereas a high density of peri-tumoral TLS (P-score high) were associated with shorter OS in these two cohorts (p = 0.003 and p = 0.03, respectively). Conclusion: The established four-gene signature efficiently identified the TLS in CCA tissues. The ab...