Spatial multimodal analysis revealed tertiary lymphoid structures as a risk stratification indicator in combined hepatocellular-cholangiocarcinoma

Xiaojie Gan; Wei Dong; Wenhua You; Dongyang Ding; Yuan Yang; Dapeng Sun; Wen Li; Wenbin Ding; Yuan Liang; Fu Yang; Weiping Zhou; Hui Dong; Shengxian Yuan

doi:10.1016/j.canlet.2023.216513

Spatial multimodal analysis revealed tertiary lymphoid structures as a risk stratification indicator in combined hepatocellular-cholangiocarcinoma

Cancer Lett. 2024 Jan 28:581:216513. doi: 10.1016/j.canlet.2023.216513. Epub 2023 Nov 28.

Authors

Xiaojie Gan¹, Wei Dong², Wenhua You³, Dongyang Ding⁴, Yuan Yang⁴, Dapeng Sun⁴, Wen Li⁴, Wenbin Ding⁴, Yuan Liang⁵, Fu Yang⁶, Weiping Zhou⁷, Hui Dong⁸, Shengxian Yuan⁹

Affiliations

¹ The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, China; Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
² The Department of Pathology, Eastern Hepatobilliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, China.
³ School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
⁴ The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, China.
⁵ School of Biological Science & Medical Engineering, Southeast University, Nanjing, 211189, China.
⁶ The Department of Medical Genetics, Naval Medical University, Shanghai, 200438, China; Shanghai Key Laboratory of Medical Bioprotection, Shanghai, 200433, China; Key Laboratory of Biological Defense, Ministry of Education, Shanghai, 200433, China. Electronic address: yangfusq1997@smmu.edu.cn.
⁷ The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, China. Electronic address: ehphwp@126.com.
⁸ The Department of Pathology, Eastern Hepatobilliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, China. Electronic address: huidongwh@126.com.
⁹ The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200438, China. Electronic address: yuanshengx@126.com.

PMID: 38036041
DOI: 10.1016/j.canlet.2023.216513

Abstract

The microenvironment created by tertiary lymphoid structures (TLSs) can support and regulate immune responses, affecting the prognosis and immune treatment of patients. Nevertheless, the actual importance of TLSs for predicting the prognosis of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients remains unclear. Herein, using spatial transcriptomic analysis, we revealed that a gene signature of TLSs specific to cHCC-CCA was associated with high-intensity immune infiltration. Then, a novel scoring system was developed to evaluate the distribution and frequency of TLSs in intra-tumoral and extra-tumoral regions (iTLS and eTLS scores) in 146 cHCC-CCA patients. iTLS score was positively associated with promising prognosis, likely due to the decreased frequency of suppressive immune cell like Tregs, and the ratio of CD163⁺ macrophages to macrophages in intra-tumoral TLSs via imaging mass cytometry, while improved prognosis is not necessarily indicated by a higher eTLS score. Overall, this study highlights the potential of TLSs as a prognostic factor and an indicator of immune therapy in cHCC-CCA.

Keywords: Combined hepatocellular-cholangiocarcinoma; Imaging mass cytometry; Prognosis; Spatial transcriptomics; Tertiary lymphoid structures.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bile Duct Neoplasms* / genetics
Bile Duct Neoplasms* / therapy
Bile Ducts, Intrahepatic
Carcinoma, Hepatocellular* / genetics
Carcinoma, Hepatocellular* / therapy
Cholangiocarcinoma* / genetics
Cholangiocarcinoma* / therapy
Humans
Liver Neoplasms* / genetics
Liver Neoplasms* / therapy
Prognosis
Risk Assessment
Tertiary Lymphoid Structures*
Tumor Microenvironment