The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody
BackgroundBased on molecular biomarkers, anti-angiogenic drugs in combination with programmed cell death protein 1 (PD-1) antibodies can screen the potentially beneficial populations with hepatocellular carcinoma (HCC) and predict the efficacy after treatment. Therefore, we aimed to study predictive...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.930096/full |
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| author | Chenxi Liu Sihui Zhu Sihui Zhu Yanbing Dong Jie Shao Jie Shao Baorui Liu Baorui Liu Jie Shen Jie Shen |
| author_facet | Chenxi Liu Sihui Zhu Sihui Zhu Yanbing Dong Jie Shao Jie Shao Baorui Liu Baorui Liu Jie Shen Jie Shen |
| author_sort | Chenxi Liu |
| collection | DOAJ |
| description | BackgroundBased on molecular biomarkers, anti-angiogenic drugs in combination with programmed cell death protein 1 (PD-1) antibodies can screen the potentially beneficial populations with hepatocellular carcinoma (HCC) and predict the efficacy after treatment. Therefore, we aimed to study predictive molecular biomarkers to improve the effectiveness of immuno-targeted combination therapy for HCC.Patients and MethodsBaseline clinical data, blood samples, and imaging data of the first evaluation after two cycles of treatment were collected for 40 patients with advanced HCC who underwent combination therapy, and then these data were compared according to the efficacy. Since 15 patients had complete hematology samples, we additionally tested the T lymphocyte subpopulations of these 15 patients and also compared them according to the efficacy. In addition, we also selected five patients who benefited the most from the combination therapy and five patients with the worst curative effect for gene detection based on survival time and efficacy evaluation. Finally, the relationship between certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, gene mutations and the response of immuno-targeted combination therapy for HCC was evaluated.ResultsThe high levels of CD3+CD4+CD279+, CD3+CD8+CD45RO+CD62L+T lymphocytes and tumor mutational burden (TMB) were associated with good efficacy of the combination therapy (P=0.03, P<0.01 and P=0.03). The high levels of CD3+CD4+CD28+ T lymphocytes were associated with poor efficacy of the combination therapy (P=0.02). The high mutation frequency of TP53 and ARID1A appeared in the non-response cohort. In addition, amplification mutation of 11q13-CCND1, FGF3, FGF4, and FGF19 was found in a patient with hyperprogression (HP).ConclusionsThe certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, and gene mutations established in this paper were potential predictive biomarkers for HCC patients treated with combination therapy. |
| first_indexed | 2024-12-11T03:31:02Z |
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| language | English |
| last_indexed | 2024-12-11T03:31:02Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-fe65d01d375f4659918f07257107c78b2022-12-22T01:22:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.930096930096The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 AntibodyChenxi Liu0Sihui Zhu1Sihui Zhu2Yanbing Dong3Jie Shao4Jie Shao5Baorui Liu6Baorui Liu7Jie Shen8Jie Shen9Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, ChinaComprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, ChinaComprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, ChinaComprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, ChinaComprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, ChinaComprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, ChinaComprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, ChinaComprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, ChinaComprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, ChinaComprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, ChinaBackgroundBased on molecular biomarkers, anti-angiogenic drugs in combination with programmed cell death protein 1 (PD-1) antibodies can screen the potentially beneficial populations with hepatocellular carcinoma (HCC) and predict the efficacy after treatment. Therefore, we aimed to study predictive molecular biomarkers to improve the effectiveness of immuno-targeted combination therapy for HCC.Patients and MethodsBaseline clinical data, blood samples, and imaging data of the first evaluation after two cycles of treatment were collected for 40 patients with advanced HCC who underwent combination therapy, and then these data were compared according to the efficacy. Since 15 patients had complete hematology samples, we additionally tested the T lymphocyte subpopulations of these 15 patients and also compared them according to the efficacy. In addition, we also selected five patients who benefited the most from the combination therapy and five patients with the worst curative effect for gene detection based on survival time and efficacy evaluation. Finally, the relationship between certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, gene mutations and the response of immuno-targeted combination therapy for HCC was evaluated.ResultsThe high levels of CD3+CD4+CD279+, CD3+CD8+CD45RO+CD62L+T lymphocytes and tumor mutational burden (TMB) were associated with good efficacy of the combination therapy (P=0.03, P<0.01 and P=0.03). The high levels of CD3+CD4+CD28+ T lymphocytes were associated with poor efficacy of the combination therapy (P=0.02). The high mutation frequency of TP53 and ARID1A appeared in the non-response cohort. In addition, amplification mutation of 11q13-CCND1, FGF3, FGF4, and FGF19 was found in a patient with hyperprogression (HP).ConclusionsThe certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, and gene mutations established in this paper were potential predictive biomarkers for HCC patients treated with combination therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.930096/fullhepatocellular carcinomaneoantigen reactive T cellsimmunotherapyPD-1 antibodybiomarker |
| spellingShingle | Chenxi Liu Sihui Zhu Sihui Zhu Yanbing Dong Jie Shao Jie Shao Baorui Liu Baorui Liu Jie Shen Jie Shen The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody Frontiers in Immunology hepatocellular carcinoma neoantigen reactive T cells immunotherapy PD-1 antibody biomarker |
| title | The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody |
| title_full | The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody |
| title_fullStr | The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody |
| title_full_unstemmed | The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody |
| title_short | The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody |
| title_sort | potential predictive biomarkers for advanced hepatocellular carcinoma treated with anti angiogenic drugs in combination with pd 1 antibody |
| topic | hepatocellular carcinoma neoantigen reactive T cells immunotherapy PD-1 antibody biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.930096/full |
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