Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing
Single-cell RNA-sequencing (scRNA-seq) presents better insights into cell behavior in the context of a complex tumor microenvironment by profiling single-cell populations. However, the mechanisms underlying treatment failure in hepatocellular carcinoma (HCC) are poorly understood. In this study, we...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-10-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323172200235X |
| _version_ | 1798035921948377088 |
|---|---|
| author | Xiaopei Hao Zhiying Zheng Hanyuan Liu Yao Zhang Junwei Kang Xiangyi Kong Dawei Rong Guangshun Sun Guoqiang Sun Li Liu Haibo Yu Weiwei Tang Xuehao Wang |
| author_facet | Xiaopei Hao Zhiying Zheng Hanyuan Liu Yao Zhang Junwei Kang Xiangyi Kong Dawei Rong Guangshun Sun Guoqiang Sun Li Liu Haibo Yu Weiwei Tang Xuehao Wang |
| author_sort | Xiaopei Hao |
| collection | DOAJ |
| description | Single-cell RNA-sequencing (scRNA-seq) presents better insights into cell behavior in the context of a complex tumor microenvironment by profiling single-cell populations. However, the mechanisms underlying treatment failure in hepatocellular carcinoma (HCC) are poorly understood. In this study, we performed deep scRNA-seq on immune cells under the isolation in peripheral blood, cancer tissues, and nearby common tissues of four HCC cases and two non-cancer controls, and 212,494 cells were included in the analysis. We identified distinct immune cell subtypes, enriched pathways for differential genes, and delineated associated developmentally relevant trajectories. APOC1 was found over-expressed in tumor-associated macrophages (TAMs) of HCC tissues than in normal tissues. Inhibition of APOC1 reversed the M2 phenotype to the M1 phenotype via the ferroptosis pathway in TAMs from HCC. Tumors in APOC1 −/− C57BL/6 mice demonstrated consistent attenuation compared to wild-type (WT) mice. Mass spectrometry results revealed that the relative proportion of M2 macrophages, B cells, and CD4+ T cells in the APOC1 −/− group exhibited a downward expression compared with the WT group, whereas CD8+ T cells, M1 macrophages, and NK cells exhibited an upward trend. Finally, APOC1 was found to be negatively correlated with the expression of PD1/PD-L1 in human HCC samples. In conclusion, the present study demonstrated that inhibiting APOC1 can promote the transformation of M2 macrophages into M1 macrophages via the ferroptosis pathway, thereby reshaping the tumor immune microenvironment and improving the anti-PD1 immunotherapy for HCC, providing a new strategy for improving the therapeutic effect of anti-PD1, and bringing new hope to HCC patients. |
| first_indexed | 2024-04-11T21:05:09Z |
| format | Article |
| id | doaj.art-9e92ec0b3aaa45f1813c3d7eae007166 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-11T21:05:09Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-9e92ec0b3aaa45f1813c3d7eae0071662022-12-22T04:03:23ZengElsevierRedox Biology2213-23172022-10-0156102463Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencingXiaopei Hao0Zhiying Zheng1Hanyuan Liu2Yao Zhang3Junwei Kang4Xiangyi Kong5Dawei Rong6Guangshun Sun7Guoqiang Sun8Li Liu9Haibo Yu10Weiwei Tang11Xuehao Wang12Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, ChinaDepartment of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaFirst Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Corresponding author.Department of Hepatobiliary Surgery, People's Hospital of Zhengzhou University, Zhengzhou, China; Corresponding author.Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China; Corresponding author.Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing, China; Corresponding author.Single-cell RNA-sequencing (scRNA-seq) presents better insights into cell behavior in the context of a complex tumor microenvironment by profiling single-cell populations. However, the mechanisms underlying treatment failure in hepatocellular carcinoma (HCC) are poorly understood. In this study, we performed deep scRNA-seq on immune cells under the isolation in peripheral blood, cancer tissues, and nearby common tissues of four HCC cases and two non-cancer controls, and 212,494 cells were included in the analysis. We identified distinct immune cell subtypes, enriched pathways for differential genes, and delineated associated developmentally relevant trajectories. APOC1 was found over-expressed in tumor-associated macrophages (TAMs) of HCC tissues than in normal tissues. Inhibition of APOC1 reversed the M2 phenotype to the M1 phenotype via the ferroptosis pathway in TAMs from HCC. Tumors in APOC1 −/− C57BL/6 mice demonstrated consistent attenuation compared to wild-type (WT) mice. Mass spectrometry results revealed that the relative proportion of M2 macrophages, B cells, and CD4+ T cells in the APOC1 −/− group exhibited a downward expression compared with the WT group, whereas CD8+ T cells, M1 macrophages, and NK cells exhibited an upward trend. Finally, APOC1 was found to be negatively correlated with the expression of PD1/PD-L1 in human HCC samples. In conclusion, the present study demonstrated that inhibiting APOC1 can promote the transformation of M2 macrophages into M1 macrophages via the ferroptosis pathway, thereby reshaping the tumor immune microenvironment and improving the anti-PD1 immunotherapy for HCC, providing a new strategy for improving the therapeutic effect of anti-PD1, and bringing new hope to HCC patients.http://www.sciencedirect.com/science/article/pii/S221323172200235XAPOC1Hepatocellular carcinomaSingle-cell RNA sequencingFerroptosisMacrophages |
| spellingShingle | Xiaopei Hao Zhiying Zheng Hanyuan Liu Yao Zhang Junwei Kang Xiangyi Kong Dawei Rong Guangshun Sun Guoqiang Sun Li Liu Haibo Yu Weiwei Tang Xuehao Wang Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing Redox Biology APOC1 Hepatocellular carcinoma Single-cell RNA sequencing Ferroptosis Macrophages |
| title | Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing |
| title_full | Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing |
| title_fullStr | Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing |
| title_full_unstemmed | Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing |
| title_short | Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing |
| title_sort | inhibition of apoc1 promotes the transformation of m2 into m1 macrophages via the ferroptosis pathway and enhances anti pd1 immunotherapy in hepatocellular carcinoma based on single cell rna sequencing |
| topic | APOC1 Hepatocellular carcinoma Single-cell RNA sequencing Ferroptosis Macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S221323172200235X |
| work_keys_str_mv | AT xiaopeihao inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT zhiyingzheng inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT hanyuanliu inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT yaozhang inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT junweikang inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT xiangyikong inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT daweirong inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT guangshunsun inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT guoqiangsun inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT liliu inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT haiboyu inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT weiweitang inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing AT xuehaowang inhibitionofapoc1promotesthetransformationofm2intom1macrophagesviatheferroptosispathwayandenhancesantipd1immunotherapyinhepatocellularcarcinomabasedonsinglecellrnasequencing |