Distinct Immune Signatures in Peripheral Blood Predict Chemosensitivity in Intrahepatic Cholangiocarcinoma Patients
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 blo...
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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. |
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AbstractList | 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. 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 chemother-apy.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 subpopu-lations and clinical response after chemotherapy,which suggests that it is practical to predict the poten-tial response before treatment by evaluating the proportions of the cell population in PBMCs. |
Author | Yuan, Zhen-Gang Zheng, Bo Wu, Jian-Min Wang, Hong-Yang Sui, Cheng-Jun Chen, Lei Li, Wei Yang, Ying-Cheng Shen, Si-Yun Wang, Kai-Ting Ma, Wen-Cong Wu, Rui Li, Zhi-Xuan Wu, Tong Shi, Xue-Bing Zhao, Yan Wu, Xuan Wang, Shan Zhu, Yan-Jing |
AuthorAffiliation | 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%Department of Hepatobiliary Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438,China%Fudan University Shanghai Cancer Center,Shanghai 200032,China%Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200433,China%Department of Laboratory Medicine,The Tenth People's Hospital of Shanghai,Tongji University,Shanghai 200072,China%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 Surg |
AuthorAffiliation_xml | – name: 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%Department of Hepatobiliary Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438,China%Fudan University Shanghai Cancer Center,Shanghai 200032,China%Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200433,China%Department of Laboratory Medicine,The Tenth People's Hospital of Shanghai,Tongji University,Shanghai 200072,China%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%Department of Oncology,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438,China |
Author_xml | – sequence: 1 givenname: Tong surname: Wu fullname: Wu, Tong organization: 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 – sequence: 2 givenname: Ying-Cheng surname: Yang fullname: Yang, Ying-Cheng organization: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 3 givenname: Bo surname: Zheng fullname: Zheng, Bo organization: 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 – sequence: 4 givenname: Xue-Bing surname: Shi fullname: Shi, Xue-Bing organization: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 5 givenname: Wei surname: Li fullname: Li, Wei organization: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 6 givenname: Wen-Cong surname: Ma fullname: Ma, Wen-Cong organization: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 7 givenname: Shan surname: Wang fullname: Wang, Shan organization: Fudan University Shanghai Cancer Center, Shanghai 200032, China – sequence: 8 givenname: Zhi-Xuan surname: Li fullname: Li, Zhi-Xuan organization: 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 – sequence: 9 givenname: Yan-Jing surname: Zhu fullname: Zhu, Yan-Jing organization: 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 – sequence: 10 givenname: Jian-Min surname: Wu fullname: Wu, Jian-Min organization: Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China – sequence: 11 givenname: Kai-Ting surname: Wang fullname: Wang, Kai-Ting organization: Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China – sequence: 12 givenname: Yan surname: Zhao fullname: Zhao, Yan organization: Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200433, China – sequence: 13 givenname: Rui surname: Wu fullname: Wu, Rui organization: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 14 givenname: Cheng-Jun surname: Sui fullname: Sui, Cheng-Jun organization: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 15 givenname: Si-Yun surname: Shen fullname: Shen, Si-Yun organization: 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 – sequence: 16 givenname: Xuan surname: Wu fullname: Wu, Xuan organization: Department of Laboratory Medicine, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072, China – sequence: 17 givenname: Lei surname: Chen fullname: Chen, Lei email: chenlei@smmu.edu.cn organization: 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 – sequence: 18 givenname: Zhen-Gang surname: Yuan fullname: Yuan, Zhen-Gang email: yuanzg@163.com organization: Department of Oncology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China – sequence: 19 givenname: Hong-Yang surname: Wang fullname: Wang, Hong-Yang email: hywangk@vip.sina.com organization: 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 |
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Keywords | Chemosensitivity Peripheral blood mononuclear cells Gemcitabine Intrahepatic cholangiocarcinoma |
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Publisher | Elsevier Ltd National Center for Liver Cancer,Shanghai 201805,China%Department of Hepatobiliary Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438,China%Fudan University Shanghai Cancer Center,Shanghai 200032,China%Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200433,China%Department of Laboratory Medicine,The Tenth People's Hospital of Shanghai,Tongji University,Shanghai 200072,China%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 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%Department of Oncology,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438,China Elsevier |
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Snippet | Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. Chemotherapy remains the main therapeutic strategy for advanced ICC patients, but... Intrahepatic cholangiocarcinoma(ICC)is the second most common liver cancer.Chemotherapy remains the main therapeutic strategy for advanced ICC patients,but... |
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SubjectTerms | Chemosensitivity Gemcitabine Intrahepatic cholangiocarcinoma Peripheral blood mononuclear cells |
Title | Distinct Immune Signatures in Peripheral Blood Predict Chemosensitivity in Intrahepatic Cholangiocarcinoma Patients |
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