{"title":"接受 TACE 加 ICIs 和抗 VEGF 抗体/TKIs 治疗的肝细胞癌的免疫指标变化：预后生物标志物分析。","authors":"Xiao-Yang Xu, Ze Wang, Chen-You Liu, Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu","doi":"10.2147/JHC.S487472","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.</p><p><strong>Materials: </strong>This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.</p><p><strong>Results: </strong>A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5-32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3<sup>-</sup>CD19<sup>+</sup> (<i>p</i>=0.004), CFB (<i>p</i>=0.027), NLR (<i>p</i><0.001) and an increase in Ig λ (<i>p</i>=0.010), Ig κ (<i>p</i>=0.037), Ig A (<i>p</i>=0.005), Ig G (<i>p</i>=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).</p><p><strong>Conclusion: </strong>The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"11 ","pages":"2019-2032"},"PeriodicalIF":4.2000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512558/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immune Indicator Changes in Hepatocellular Carcinoma Undergoing TACE Plus ICIs and Anti-VEGF Antibodies/TKIs: A Prognostic Biomarker Analysis.\",\"authors\":\"Xiao-Yang Xu, Ze Wang, Chen-You Liu, Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu\",\"doi\":\"10.2147/JHC.S487472\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.</p><p><strong>Materials: </strong>This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.</p><p><strong>Results: </strong>A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5-32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3<sup>-</sup>CD19<sup>+</sup> (<i>p</i>=0.004), CFB (<i>p</i>=0.027), NLR (<i>p</i><0.001) and an increase in Ig λ (<i>p</i>=0.010), Ig κ (<i>p</i>=0.037), Ig A (<i>p</i>=0.005), Ig G (<i>p</i>=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).</p><p><strong>Conclusion: </strong>The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.</p>\",\"PeriodicalId\":15906,\"journal\":{\"name\":\"Journal of Hepatocellular Carcinoma\",\"volume\":\"11 \",\"pages\":\"2019-2032\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-10-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512558/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Hepatocellular Carcinoma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/JHC.S487472\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hepatocellular Carcinoma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JHC.S487472","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的探讨接受TACE+免疫检查点抑制剂（ICIs）和抗VEGF抗体/TKIs治疗的肝细胞癌（HCC）患者循环免疫指标的变化趋势，并阐明免疫反应与肿瘤预后之间的关系：这项单中心回顾性研究纳入了2019年3月11日至2024年2月15日期间接受TACE+ICIs和抗VEGF抗体/TKIs治疗的不可切除HCC患者。在基线和每个周期采集外周血样本，分析其中的血细胞计数和免疫指标。主要结果是首次评估时的客观反应率（ORR）。根据基于 mRECIST 的首次评估结果，将患者分为 PD 组、SD 组和 OR 组进行分析。根据首次评估后是否出现进展，对OR组进行进一步的亚组分析。淋巴细胞亚群通过流式细胞术进行测量。免疫球蛋白采用免疫比浊法进行测量。中性粒细胞与淋巴细胞比值（NLR）通过全血细胞计数法测量。采用简单线性回归分析动态趋势：共有 63 名患者入组，首次评估时 ORR 为 55.6%，疾病控制率 (DCR) 为 87.3%。中位总生存期（mOS）为27.5个月（95% CI：22.5-32.5个月）。在 OR 组（n=35）中，更活跃的免疫反应（表现为 CD3-CD19+ (p=0.004)、CFB (p=0.027)、NLR (pp=0.010)、Ig κ (p=0.037)、Ig A (p=0.005)、Ig G (p=0.006)的下降）与更好的预后有关，而在 OR-nPD 亚组中也出现了类似的模式。同时，PD 组（n=8）无明显差异：结论：联合治疗可改变 HCC 的肿瘤微环境。循环免疫指标和 NLR 的变化趋势可作为预测肿瘤反应和指导临床治疗的潜在生物标志物。
Immune Indicator Changes in Hepatocellular Carcinoma Undergoing TACE Plus ICIs and Anti-VEGF Antibodies/TKIs: A Prognostic Biomarker Analysis.
Objective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.
Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.
Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5-32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3-CD19+ (p=0.004), CFB (p=0.027), NLR (p<0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).
Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.
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