Distinct Immune Signatures in Peripheral Blood Predict Chemosensitivity in Intrahepatic Cholangiocarcinoma Patients

Engineering ›› 2021, Vol. 7 ›› Issue (10) : 1381 -1393. DOI: 10.1016/j.eng.2021.01.014

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^{a I} nternational Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai 200438, China

^b National Center for Liver Cancer, Shanghai 201805, China

^c Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

^d Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

^e Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China

^f Department of Laboratory Medicine, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072, China

^g Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Shanghai 200438, China

^h Department of Oncology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

ⁱ Shanghai Key Laboratory of Hepato-biliary Tumor Biology, Shanghai 200438, China

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Received	Accepted	Published
2020-05-25		2021-01-24
Issue Date	Revised Date
2024-06-14

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Abstract

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. Chemotherapy remains the main therapeutic strategy for advanced ICC patients, but chemosensitivity varies individually. Here, we applied cytometry by time-of-flight (CyTOF) to establish the immune profile of peripheral blood mononuclear cells (PBMCs) on the single-cell level at indicated time points before, during, and after chemotherapy. Multiplex immunofluorescence staining was applied to examine the spatial distribution of certain immune clusters. Tissue microarrays (TMAs) were used for prognostic evaluation. A total of 20 ICC patients treated with gemcitabine (GEM) were enrolled in our study, including eight cases with good response (R) and 12 cases with non-response (NR). Tremendous changes in PBMC composition, including an increased level of CD4/CD8 double-positive T cells (DPT), were observed after chemotherapy. Patients with higher level of CD4⁺CD45RO⁺CXCR3⁺ T cells before treatment had a favorable response to chemotherapy. Our study identified a positive correlation between the percentage of T cell subpopulations and clinical response after chemotherapy, which suggests that it is practical to predict the potential response before treatment by evaluating the proportions of the cell population in PBMCs.

Keywords

Intrahepatic cholangiocarcinoma / Gemcitabine / Chemosensitivity / Peripheral blood mononuclear cells

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Tong Wu, Ying-Cheng Yang, Bo Zheng, Xue-Bing Shi, Wei Li, Wen-Cong Ma, Shan Wang, Zhi-Xuan Li, Yan-Jing Zhu, Jian-Min Wu, Kai-Ting Wang, Yan Zhao, Rui Wu, Cheng-Jun Sui, Si-Yun Shen, Xuan Wu, Lei Chen, Zhen-Gang Yuan, Hong-Yang Wang. Distinct Immune Signatures in Peripheral Blood Predict Chemosensitivity in Intrahepatic Cholangiocarcinoma Patients. Engineering, 2021, 7(10): 1381-1393 DOI:10.1016/j.eng.2021.01.014