Distinct Immune Signatures in Peripheral Blood Predict Chemosensitivity in Intrahepatic Cholangiocarcinoma Patients
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
Affiliations
Tong Wu
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai 201805, China
Ying-Cheng Yang
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Bo Zheng
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai 201805, China
Xue-Bing Shi
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Wei Li
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Wen-Cong Ma
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Shan Wang
Fudan University Shanghai Cancer Center, Shanghai 200032, China
Zhi-Xuan Li
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai 201805, China
Yan-Jing Zhu
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai 201805, China
Jian-Min Wu
Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China
Kai-Ting Wang
Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China
Yan Zhao
Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China
Rui Wu
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Cheng-Jun Sui
Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Si-Yun Shen
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; National Center for Liver Cancer, Shanghai 201805, China
Xuan Wu
Department of Laboratory Medicine, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072, China
Lei Chen
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Fudan University Shanghai Cancer Center, Shanghai 200032, China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Shanghai 200438, China; Corresponding authors.
Zhen-Gang Yuan
Department of Oncology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Corresponding authors.
Hong-Yang Wang
International Cooperation Laboratory on Signal Transduction & Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education & Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China; Fudan University Shanghai Cancer Center, Shanghai 200032, China; Corresponding authors.
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.
