Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma
LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role...
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.810269/full |
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| author | Qing Yan Qing Yan Hao-Ming Lin Ke Zhu Yi Cao Xiao-Lin Xu Zi-Yu Zhou Lei-bo Xu Chao Liu Rui Zhang |
| author_facet | Qing Yan Qing Yan Hao-Ming Lin Ke Zhu Yi Cao Xiao-Lin Xu Zi-Yu Zhou Lei-bo Xu Chao Liu Rui Zhang |
| author_sort | Qing Yan |
| collection | DOAJ |
| description | LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P<0.001) and distant metastasis(P=0.020) in FGL1 positive patients was higher than that of FGL1 negative patients. In addition, patients with FGL1 positive circulating tumor cells had worse postoperative survival than FGL1 negative patients (p=0.0297). The mixed phenotypic CTC presented a higher level of FGL1 expression than any other types, the number of which also predicted worse prognosis(p=0.0443). We also found that the expression of FGL1 on CTCs was associated with the level of FGL1 in tumor tissues. Of 12 patients receiving PD-1/PD-L1 blockade in a total of 109 cases, 8 out of 10 patients with FGL1 positive CTC showed immunotherapy resistance. It is the first study that suggested FGL1 expression in CTCs as an indicator of the poor prognosis in HCC patients. CTC detection may serve as a promising replacement for determination of tumor tissue FGL1 expression and provide evidence for the application of immunotherapy. |
| first_indexed | 2024-12-23T23:56:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-23T23:56:24Z |
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| series | Frontiers in Oncology |
| spelling | doaj.art-e1088f12288647cd8c68bfdbb467756d2022-12-21T17:25:14ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.810269810269Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular CarcinomaQing Yan0Qing Yan1Hao-Ming Lin2Ke Zhu3Yi Cao4Xiao-Lin Xu5Zi-Yu Zhou6Lei-bo Xu7Chao Liu8Rui Zhang9Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Hepatic Surgery, The First People’s Hospital of Foshan, Foshan, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaLAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P<0.001) and distant metastasis(P=0.020) in FGL1 positive patients was higher than that of FGL1 negative patients. In addition, patients with FGL1 positive circulating tumor cells had worse postoperative survival than FGL1 negative patients (p=0.0297). The mixed phenotypic CTC presented a higher level of FGL1 expression than any other types, the number of which also predicted worse prognosis(p=0.0443). We also found that the expression of FGL1 on CTCs was associated with the level of FGL1 in tumor tissues. Of 12 patients receiving PD-1/PD-L1 blockade in a total of 109 cases, 8 out of 10 patients with FGL1 positive CTC showed immunotherapy resistance. It is the first study that suggested FGL1 expression in CTCs as an indicator of the poor prognosis in HCC patients. CTC detection may serve as a promising replacement for determination of tumor tissue FGL1 expression and provide evidence for the application of immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.810269/fullcirculating tumor cellsFGL1hepatocellular carcinoma (HCC)immunotherapyclinical application |
| spellingShingle | Qing Yan Qing Yan Hao-Ming Lin Ke Zhu Yi Cao Xiao-Lin Xu Zi-Yu Zhou Lei-bo Xu Chao Liu Rui Zhang Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma Frontiers in Oncology circulating tumor cells FGL1 hepatocellular carcinoma (HCC) immunotherapy clinical application |
| title | Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma |
| title_full | Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma |
| title_fullStr | Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma |
| title_full_unstemmed | Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma |
| title_short | Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma |
| title_sort | immune checkpoint fgl1 expression of circulating tumor cells is associated with poor survival in curatively resected hepatocellular carcinoma |
| topic | circulating tumor cells FGL1 hepatocellular carcinoma (HCC) immunotherapy clinical application |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.810269/full |
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