Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy
Background Despite the success of immune checkpoint inhibitor (ICI)-based combination therapies in hepatocellular carcinoma (HCC), its effectiveness remains confined to a subset of patients. The development of reliable, predictive markers is important for accurate patient stratification and further...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-11-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/11/e010534.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850175938106490880 |
|---|---|
| author | Xiaobo Li Chang Xu Mingjie Zhang Shengnan Guo Dapeng Hao Changqing Liu Jing Ren Guangyu Wang Cheng Lyu Tianhao Li Huanhuan Xu Zepeng Hou Mingshuo Zhang Dan Kong |
| author_facet | Xiaobo Li Chang Xu Mingjie Zhang Shengnan Guo Dapeng Hao Changqing Liu Jing Ren Guangyu Wang Cheng Lyu Tianhao Li Huanhuan Xu Zepeng Hou Mingshuo Zhang Dan Kong |
| author_sort | Xiaobo Li |
| collection | DOAJ |
| description | Background Despite the success of immune checkpoint inhibitor (ICI)-based combination therapies in hepatocellular carcinoma (HCC), its effectiveness remains confined to a subset of patients. The development of reliable, predictive markers is important for accurate patient stratification and further mechanistic understanding of therapy response.Methods We comprehensively analyzed paired single-cell RNA transcriptome and T-cell repertoire profiles from 14 HCC ascites samples, collected from 7 patients before and after treatment with the combination of sintilimab (anti-PD-1) and bevacizumab (anti-VEGF).Results We identify a widespread convergence on interferon (IFN) signaling across various immune cell lineages in treatment-responsive patients with HCC, indicating a common transcriptional state transition in the immune microenvironment linked to immunotherapy response in HCC. Strong IFN signaling marks CD8+ T cells with larger clonal expansion and enhanced cytotoxicity, macrophages toward M1-like polarization and strong T-cell recruitment ability, dendritic cells with increased antigen presentation capacity, as well as highly cytotoxic natural killer cells and activated B cells. By translating our finding to cohorts of patients with HCC, we demonstrate the specificity of IFN-signaling in the prognosis of patients with HCC and its ability to predict immunotherapy response.Conclusions This study provides a unique single-cell resource with clonal and longitudinal resolution during ICI therapy and reveals IFN signaling as a biomarker of immunotherapy response in HCC, suggesting a beneficial effect by combining IFN inducers with ICIs for patients with HCC. |
| format | Article |
| id | doaj-art-71fbdeeb7b084c8a914ce3bc2f25ec63 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-71fbdeeb7b084c8a914ce3bc2f25ec632025-08-20T02:19:22ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-11-01121110.1136/jitc-2024-010534Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapyXiaobo Li0Chang Xu1Mingjie Zhang2Shengnan Guo3Dapeng Hao4Changqing Liu5Jing Ren6Guangyu Wang7Cheng Lyu8Tianhao Li9Huanhuan Xu10Zepeng Hou11Mingshuo Zhang12Dan Kong13School of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaSchool of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaSchool of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaDepartment of Phase 1 Trials Center, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaDepartment of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaSchool of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaDepartment of Phase 1 Trials Center, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaSchool of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaSchool of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaSchool of Basic Medical Sciences, Harbin Medical University, Harbin, People`s Republic of ChinaDepartment of Gynecologic Oncology, Harbin Medical University Cancer Hospital, Harbin, People`s Republic of ChinaBackground Despite the success of immune checkpoint inhibitor (ICI)-based combination therapies in hepatocellular carcinoma (HCC), its effectiveness remains confined to a subset of patients. The development of reliable, predictive markers is important for accurate patient stratification and further mechanistic understanding of therapy response.Methods We comprehensively analyzed paired single-cell RNA transcriptome and T-cell repertoire profiles from 14 HCC ascites samples, collected from 7 patients before and after treatment with the combination of sintilimab (anti-PD-1) and bevacizumab (anti-VEGF).Results We identify a widespread convergence on interferon (IFN) signaling across various immune cell lineages in treatment-responsive patients with HCC, indicating a common transcriptional state transition in the immune microenvironment linked to immunotherapy response in HCC. Strong IFN signaling marks CD8+ T cells with larger clonal expansion and enhanced cytotoxicity, macrophages toward M1-like polarization and strong T-cell recruitment ability, dendritic cells with increased antigen presentation capacity, as well as highly cytotoxic natural killer cells and activated B cells. By translating our finding to cohorts of patients with HCC, we demonstrate the specificity of IFN-signaling in the prognosis of patients with HCC and its ability to predict immunotherapy response.Conclusions This study provides a unique single-cell resource with clonal and longitudinal resolution during ICI therapy and reveals IFN signaling as a biomarker of immunotherapy response in HCC, suggesting a beneficial effect by combining IFN inducers with ICIs for patients with HCC.https://jitc.bmj.com/content/12/11/e010534.full |
| spellingShingle | Xiaobo Li Chang Xu Mingjie Zhang Shengnan Guo Dapeng Hao Changqing Liu Jing Ren Guangyu Wang Cheng Lyu Tianhao Li Huanhuan Xu Zepeng Hou Mingshuo Zhang Dan Kong Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy Journal for ImmunoTherapy of Cancer |
| title | Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy |
| title_full | Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy |
| title_fullStr | Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy |
| title_full_unstemmed | Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy |
| title_short | Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy |
| title_sort | integrated single cell transcriptome and tcr profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy |
| url | https://jitc.bmj.com/content/12/11/e010534.full |
| work_keys_str_mv | AT xiaoboli integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT changxu integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT mingjiezhang integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT shengnanguo integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT dapenghao integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT changqingliu integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT jingren integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT guangyuwang integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT chenglyu integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT tianhaoli integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT huanhuanxu integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT zepenghou integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT mingshuozhang integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy AT dankong integratedsinglecelltranscriptomeandtcrprofilesofhepatocellularcarcinomahighlighttheconvergenceoninterferonsignalingduringimmunotherapy |