Tertiary lymphoid structures predict the prognosis and immunotherapy response of cholangiocarcinoma

Frontiers in Immunology

Immunology

Feiling Feng¹  Xin Li²  Hui Wang²  Hui Dong³  Tao Lu³  Tianyi Jiang⁴  Yufei Pan⁴  Xiaofan Feng⁴  Xiaowen Cui⁴  Zhiwen Ding⁴  Mengyou Xu⁴  Yexiong Tan⁴  Yunkai Lin⁴  Mengmiao Pei⁵  Liwei Dong⁶  Taiyu Shang⁷  Hongyang Wang⁸ 

[1] Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China;Department of Hepatobiliary Diseases, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China;Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China;National Center for Liver Cancer, Naval Medical University, Shanghai, China;National Center for Liver Cancer, Naval Medical University, Shanghai, China;Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China;National Center for Liver Cancer, Naval Medical University, Shanghai, China;International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China;National Center for Liver Cancer, Naval Medical University, Shanghai, China;School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China;National Center for Liver Cancer, Naval Medical University, Shanghai, China;School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China;International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Shanghai, China;

关键词: cholangiocarcinoma;    tertiary lymphoid structures;    tumor microenvironment;    immune checkpoint inhibitors;    prognosis;   

DOI  :  10.3389/fimmu.2023.1166497

 received in 2023-02-15, accepted in 2023-04-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionCholangiocarcinoma (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.MethodsWe 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.ResultsDifferent 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).ConclusionThe established four-gene signature efficiently identified the TLS in CCA tissues. The abundance and spatial distribution of TLS were significantly correlated with the prognosis and immune checkpoint inhibitors (ICIs) immunotherapy response of CCA patients. The presence of intra-tumoral TLS are positive prognostic factors for CCA, which provide a theoretical basis for the future diagnosis and treatment of CCA.

【 授权许可】

Unknown   
Copyright © 2023 Shang, Jiang, Lu, Wang, Cui, Pan, Xu, Pei, Ding, Feng, Lin, Li, Tan, Feng, Dong, Wang and Dong