A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer
Background: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01066/full |
| _version_ | 1819067338165583872 |
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| author | Xi Li Xi Li Xi Li Rouzheng Wang Rouzheng Wang Rouzheng Wang Peiwen Fan Peiwen Fan Xuan Yao Xuan Yao Ling Qin Yanchun Peng Yanchun Peng Miaomiao Ma Miaomiao Ma Neil Asley Xuimei Chang Xuimei Chang Yaning Feng Yaning Feng Yunhui Hu Yunhui Hu Yonghong Zhang Chris Li Gregory Fanning Stephanie Jones Clare Verrill David Maldonado-Perez Paul Sopp Craig Waugh Stephen Taylor Simon Mcgowan Vincenzo Cerundolo Vincenzo Cerundolo Christopher Conlon Andrew McMichael Shichun Lu Xiyan Wang Xiyan Wang Ning Li Tao Dong Tao Dong |
| author_facet | Xi Li Xi Li Xi Li Rouzheng Wang Rouzheng Wang Rouzheng Wang Peiwen Fan Peiwen Fan Xuan Yao Xuan Yao Ling Qin Yanchun Peng Yanchun Peng Miaomiao Ma Miaomiao Ma Neil Asley Xuimei Chang Xuimei Chang Yaning Feng Yaning Feng Yunhui Hu Yunhui Hu Yonghong Zhang Chris Li Gregory Fanning Stephanie Jones Clare Verrill David Maldonado-Perez Paul Sopp Craig Waugh Stephen Taylor Simon Mcgowan Vincenzo Cerundolo Vincenzo Cerundolo Christopher Conlon Andrew McMichael Shichun Lu Xiyan Wang Xiyan Wang Ning Li Tao Dong Tao Dong |
| author_sort | Xi Li |
| collection | DOAJ |
| description | Background: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-blockade or combinatorial blockade regimens may reinvigorate antitumor T-cell immunity in those cancer patients while limiting immune-related adverse effects.Method: This study recruited, in total, 172 primary cancer patients (131 were blood-tumor-matched patients) who were treatment-naïve prior to the surgeries or biopsies covering the eight most prevalent types of cancer. With access to fresh surgical samples, this study simultaneously investigated the ex vivo expression level of eight known immune checkpoint receptors [PD-1, cytotoxic T-lymphocyte antigen-4 [CTLA-4], T-cell immunoglobulin and mucin-domain containing-3 [Tim-3], 2B4, killer cell lectin like receptor G1 [KLRG-1], TIGIT, B- and T-lymphocyte attenuator [BTLA], and CD160] on tumor-infiltrating T cells (TILs) and paired circulating T cells in blood from a 131-patient cohort.Results: We found increased an expression of PD-1 and Tim-3 but a decreased expression of BTLA on TILs when compared with peripheral blood from multiple types of cancer. Moreover, our co-expression analysis of key immune checkpoint receptors delineates “shared” subsets as PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4– and PD-1+TIGIT+2B4+Tim-3–KLRG-1–CTLA-4– from bulk CD8 TILs. Furthermore, we found that a higher frequency of advanced differentiation stage T cells (CD27–CCR7–CD45RA–) among the “shared” subset (PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4–) in bulk CD8 TILs was associated with poorly differentiated cancer type in cervical cancer patients.Conclusions: To our knowledge, our study is the first comprehensive analysis of key immune checkpoint receptors on T cells in treatment-naïve, primary cancer patients from the eight most prevalent types of cancer. These findings might provide useful information for future design of mono-blockade/combinatorial blockades and/or genetically modified T-cell immunotherapy. |
| first_indexed | 2024-12-21T16:16:40Z |
| format | Article |
| id | doaj.art-772c0dafccf74a729e4b3727ac88843d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T16:16:40Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-772c0dafccf74a729e4b3727ac88843d2022-12-21T18:57:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-10-01910.3389/fonc.2019.01066472080A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of CancerXi Li0Xi Li1Xi Li2Rouzheng Wang3Rouzheng Wang4Rouzheng Wang5Peiwen Fan6Peiwen Fan7Xuan Yao8Xuan Yao9Ling Qin10Yanchun Peng11Yanchun Peng12Miaomiao Ma13Miaomiao Ma14Neil Asley15Xuimei Chang16Xuimei Chang17Yaning Feng18Yaning Feng19Yunhui Hu20Yunhui Hu21Yonghong Zhang22Chris Li23Gregory Fanning24Stephanie Jones25Clare Verrill26David Maldonado-Perez27Paul Sopp28Craig Waugh29Stephen Taylor30Simon Mcgowan31Vincenzo Cerundolo32Vincenzo Cerundolo33Christopher Conlon34Andrew McMichael35Shichun Lu36Xiyan Wang37Xiyan Wang38Ning Li39Tao Dong40Tao Dong41Key Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomBeijing You'an Hospital, Capital Medical University, Beijing, ChinaNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaSingle Cell Genomics Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaBeijing You'an Hospital, Capital Medical University, Beijing, ChinaChina R&D, Janssen Pharmaceuticals, Shanghai, ChinaChina R&D, Janssen Pharmaceuticals, Shanghai, ChinaOxford Radcliffe Biobank, Department of Cellular Pathology, Oxford University Hospitals NHS Trust, Oxford, United KingdomNuffield Department of Surgical Sciences, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United KingdomNuffield Department of Surgical Sciences, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom0Flow Cytometry Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom0Flow Cytometry Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom1Bioinformatics Team, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom1Bioinformatics Team, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United Kingdom2China Military General Hospital, Beijing, ChinaKey Laboratory of Tumor Immunology and Radiation Therapy, Third Affiliated Hospital, Xinjiang Tumor Hospital, Chinese Academy of Medical Sciences (CAMS), Xinjiang Medical University, Ürümqi, ChinaThird Affiliated Hospital, Xinjiang Tumor Hospital, Xinjiang Medical University, Ürümqi, ChinaBeijing You'an Hospital, Capital Medical University, Beijing, ChinaNuffield Department of Medicine (NDM), Chinese Academy of Medical Sciences Oxford Institute (CAMS Oxford Institute), University of Oxford, Oxford, United KingdomMRC Human Immunology Unit, Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomBackground: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-blockade or combinatorial blockade regimens may reinvigorate antitumor T-cell immunity in those cancer patients while limiting immune-related adverse effects.Method: This study recruited, in total, 172 primary cancer patients (131 were blood-tumor-matched patients) who were treatment-naïve prior to the surgeries or biopsies covering the eight most prevalent types of cancer. With access to fresh surgical samples, this study simultaneously investigated the ex vivo expression level of eight known immune checkpoint receptors [PD-1, cytotoxic T-lymphocyte antigen-4 [CTLA-4], T-cell immunoglobulin and mucin-domain containing-3 [Tim-3], 2B4, killer cell lectin like receptor G1 [KLRG-1], TIGIT, B- and T-lymphocyte attenuator [BTLA], and CD160] on tumor-infiltrating T cells (TILs) and paired circulating T cells in blood from a 131-patient cohort.Results: We found increased an expression of PD-1 and Tim-3 but a decreased expression of BTLA on TILs when compared with peripheral blood from multiple types of cancer. Moreover, our co-expression analysis of key immune checkpoint receptors delineates “shared” subsets as PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4– and PD-1+TIGIT+2B4+Tim-3–KLRG-1–CTLA-4– from bulk CD8 TILs. Furthermore, we found that a higher frequency of advanced differentiation stage T cells (CD27–CCR7–CD45RA–) among the “shared” subset (PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4–) in bulk CD8 TILs was associated with poorly differentiated cancer type in cervical cancer patients.Conclusions: To our knowledge, our study is the first comprehensive analysis of key immune checkpoint receptors on T cells in treatment-naïve, primary cancer patients from the eight most prevalent types of cancer. These findings might provide useful information for future design of mono-blockade/combinatorial blockades and/or genetically modified T-cell immunotherapy.https://www.frontiersin.org/article/10.3389/fonc.2019.01066/fullT cellsinhibitory receptortumor-infiltrating lymphocytestumor microenvironmentcombinatorial checkpoint blockade |
| spellingShingle | Xi Li Xi Li Xi Li Rouzheng Wang Rouzheng Wang Rouzheng Wang Peiwen Fan Peiwen Fan Xuan Yao Xuan Yao Ling Qin Yanchun Peng Yanchun Peng Miaomiao Ma Miaomiao Ma Neil Asley Xuimei Chang Xuimei Chang Yaning Feng Yaning Feng Yunhui Hu Yunhui Hu Yonghong Zhang Chris Li Gregory Fanning Stephanie Jones Clare Verrill David Maldonado-Perez Paul Sopp Craig Waugh Stephen Taylor Simon Mcgowan Vincenzo Cerundolo Vincenzo Cerundolo Christopher Conlon Andrew McMichael Shichun Lu Xiyan Wang Xiyan Wang Ning Li Tao Dong Tao Dong A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer Frontiers in Oncology T cells inhibitory receptor tumor-infiltrating lymphocytes tumor microenvironment combinatorial checkpoint blockade |
| title | A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer |
| title_full | A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer |
| title_fullStr | A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer |
| title_full_unstemmed | A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer |
| title_short | A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer |
| title_sort | comprehensive analysis of key immune checkpoint receptors on tumor infiltrating t cells from multiple types of cancer |
| topic | T cells inhibitory receptor tumor-infiltrating lymphocytes tumor microenvironment combinatorial checkpoint blockade |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01066/full |
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