Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia

被引:569
作者
Zhou, Qing [1 ,2 ]
Munger, Meghan E. [1 ,2 ]
Veenstra, Rachelle G. [1 ,2 ]
Weigel, Brenda J. [1 ,2 ]
Hirashima, Mitsuomi [3 ]
Munn, David H. [4 ]
Murphy, William J. [5 ]
Azuma, Miyuki [6 ]
Anderson, Ana C. [7 ]
Kuchroo, Vijay K. [7 ]
Blazar, Bruce R. [1 ,2 ]
机构
[1] Kagawa Univ, Fac Med, Massey Canc Ctr, Kagawa, Japan
[2] Kagawa Univ, Fac Med, Dept Pediat, Div Hematol Oncol & Blood & Marrow Transplantat, Kagawa, Japan
[3] Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, Kagawa, Japan
[4] Med Coll Georgia, Dept Pediat, Sch Med, Augusta, GA 30912 USA
[5] Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA
[6] Tokyo Med & Dent Univ, Dept Mol Immunol, Tokyo, Japan
[7] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Sch Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
CHRONIC VIRAL-INFECTION; ACUTE MYELOID-LEUKEMIA; GALECTIN-9; SUPPRESSES; DISEASE PROGRESSION; ANTITUMOR IMMUNITY; UP-REGULATION; EXPRESSION; INDUCTION; RESPONSES; BINDING;
D O I
10.1182/blood-2010-10-310425
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Tumor-associated immune suppression can lead to defective T cell-mediated antitumor immunity. Here, we identified a unique phenotype of exhausted T cells in mice with advanced acute myelogenous leukemia (AML). This phenotype is characterized by the coexpression of Tim-3 and PD-1 on CD8(+) T cells in the liver, the major first site of AML metastases. PD-1 and Tim-3 coexpression increased during AML progression. PD-1(+)Tim-3(+) CD8(+) T cells were deficient in their ability to produce IFN-gamma, TNF-alpha, and IL-2 in response to PD-1 ligand (PDL1) and Tim-3 ligand (galectin-9) expressing AML cells. PD-1 knockout (KO), which were partially resistant to AML challenge, up-regulated Tim-3 during AML progression and such Tim-3(+)PD-1- KO CD8(+) T cells had reduced cytokine production. Galectin-9 KO mice were more resistant to AML, which was associated with reduced T-regulatory cell accumulation and a modest induction of PD-1 and Tim-3 expression on CD8(+) T cells. Whereas blocking the PD-1/PDL1 or Tim-3/galectin-9 pathway alone was insufficient to rescue mice from AML lethality, an additive effect was seen in reducing-albeit not eliminating-both tumor burden and lethality when both pathways were blocked. Therefore, combined PD-1/PDL1 and Tim-3/galectin-9 blockade may be beneficial in preventing CD8(+) T-cell exhaustion in patients with hematologic malignancies such as advanced AML. (Blood. 2011; 117(17):4501-4510)
引用
收藏
页码:4501 / 4510
页数:10
相关论文
共 50 条
[41]   Divergent fates of antigen-specific CD8+ T cell clones in mice with acute leukemia [J].
Chen, Xiufen ;
MacNabb, Brendan W. ;
Flood, Blake ;
Blazar, Bruce R. ;
Kline, Justin .
CELL REPORTS, 2021, 37 (06)
[42]   Upregulation of TIM-3 and PD-1 on CD4+and CD8+T Cells Associated with Dysfunction of Cell-Mediated Immunity after Colorectal Cancer Operation [J].
Arai, Yosuke ;
Saito, Hiroaki ;
Ikeguchi, Masahide .
YONAGO ACTA MEDICA, 2012, 55 (01) :1-9
[43]   Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia [J].
Jiaxiong Tan ;
Shaohua Chen ;
Yuhong Lu ;
Danlin Yao ;
Ling Xu ;
Yikai Zhang ;
Lijian Yang ;
Jie Chen ;
Jing Lai ;
Zhi Yu ;
Kanger Zhu ;
Yangqiu Li .
ChineseJournalofCancerResearch, 2017, 29 (05) :463-470
[44]   Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells [J].
Granier, Clemence ;
Vinatier, Emeline ;
Colin, Elia ;
Mandavit, Marion ;
Dariane, Charles ;
Verkarre, Virginie ;
Biard, Lucie ;
El Zein, Rami ;
Lesaffre, Corinne ;
Galy-Fauroux, Isabelle ;
Roussel, Helene ;
De Guillebon, Eleonore ;
Blanc, Charlotte ;
Saldmann, Antonin ;
Badoual, Cecile ;
Gey, Alain ;
Tartour, Eric .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2018, (132)
[45]   CD8+ T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients [J].
Wang, Mengjie ;
Bu, Jin ;
Zhou, Maohua ;
Sido, Jessica ;
Lin, Yu ;
Liu, Guanfang ;
Lin, Qiwen ;
Xu, Xiuzhang ;
Leavenworth, Jianmei W. ;
Shen, Erxia .
CLINICAL IMMUNOLOGY, 2018, 190 :64-73
[46]   PD-1 Is a Regulator of NY-ESO-1-Specific CD8+ T Cell Expansion in Melanoma Patients [J].
Fourcade, Julien ;
Kudela, Pavol ;
Sun, Zhaojun ;
Shen, Hongmei ;
Land, Stephanie R. ;
Lenzner, Diana ;
Guillaume, Philippe ;
Luescher, Immanuel F. ;
Sander, Cindy ;
Ferrone, Soldano ;
Kirkwood, John M. ;
Zarour, Hassane M. .
JOURNAL OF IMMUNOLOGY, 2009, 182 (09) :5240-5249
[47]   The Role of LAT in Increased CD8+ T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1 [J].
Allen, Sariah J. ;
Hamrah, Pedram ;
Gate, David ;
Mott, Kevin R. ;
Mantopoulos, Dimosthenis ;
Zheng, Lixin ;
Town, Terrence ;
Jones, Clinton ;
von Andrian, Ulrich H. ;
Freeman, Gordon J. ;
Sharpe, Arlene H. ;
BenMohamed, Lbachir ;
Ahmed, Rafi ;
Wechsler, Steven L. ;
Ghiasi, Homayon .
JOURNAL OF VIROLOGY, 2011, 85 (09) :4184-4197
[48]   Tim-3 Directly Enhances CD8 T Cell Responses to Acute Listeria monocytogenes Infection [J].
Gorman, Jacob V. ;
Starbeck-Miller, Gabriel ;
Pham, Nhat-Long L. ;
Traver, Geri L. ;
Rothman, Paul B. ;
Harty, John T. ;
Colgan, John D. .
JOURNAL OF IMMUNOLOGY, 2014, 192 (07) :3133-3142
[49]   CD8+ T-Cell Exhaustion Phenotype in Chronic Hepatitis C Virus Infection Is Associated With Epitope Sequence Variation [J].
Osuch, Sylwia ;
Laskus, Tomasz ;
Perlejewski, Karol ;
Berak, Hanna ;
Bukowska-Osko, Iwona ;
Pollak, Agnieszka ;
Zielenkiewicz, Magdalena ;
Radkowski, Marek ;
Caraballo Cortes, Kamila .
FRONTIERS IN IMMUNOLOGY, 2022, 13
[50]   Elevated Expression of Tim-3 and PD-1 Immune Checkpoint Receptors on T-CD4+ Lymphocytes of Patients with Asthma [J].
Mosayebian, Ali ;
Koohini, Zohreh ;
Hossein-Nataj, Hadi ;
Abediankenari, Saeid ;
Abedi, Siavash ;
Asgarian-Omran, Hossein .
IRANIAN JOURNAL OF ALLERGY ASTHMA AND IMMUNOLOGY, 2018, 17 (06) :517-525