CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8+ T Cells

被引：132

作者：

Braun, Matthias ^{[1
,2
]}

Aguilera, Amelia Roman ^{[1
]}

Sundarrajan, Ashmitha ^{[2
]}

Corvino, Dillon ^{[2
]}

Stannard, Kimberley ^{[1
,2
]}

Krumeich, Sophie ^{[2
]}

Das, Indrajit ^{[1
]}

Lima, Luize G. ^{[3
]}

Guzman, Lizeth G. Meza ^{[4
,5
]}

Li, Kunlun ^{[4
,5
]}

Li, Rui ^{[6
,7
]}

Salim, Nazhifah ^{[2
]}

Jorge, Maria Villancanas ^{[2
]}

Ham, Sunyoung ^{[3
]}

Kelly, Gabrielle ^{[1
]}

Vari, Frank ^{[1
]}

Lepletier, Ailin ^{[1
]}

Raghavendra, Ashwini ^{[1
]}

Pearson, Sally ^{[1
]}

Madore, Jason ^{[1
]}

Jacquelin, Sebastien ^{[9
]}

Effern, Maike ^{[10
,11
]}

Quine, Brodie ^{[1
,2
]}

Koufariotis, Lambros T. ^{[12
]}

Casey, Mika ^{[1
]}

Nakamura, Kyohei ^{[1
]}

Seo, Eun Y. ^{[13
]}

Holzel, Michael ^{[10
]}

Geyer, Matthias ^{[14
]}

Kristiansen, Glen ^{[15
]}

Taheri, Touraj ^{[16
]}

Ahern, Elizabeth ^{[1
,17
]}

Hughes, Brett G. M. ^{[17
]}

Wilmott, James S. ^{[18
,19
]}

Long, Georgina V. ^{[18
,19
,20
,21
]}

Scolyer, Richard A. ^{[18
,22
]}

Batstone, Martin D. ^{[17
]}

Landsberg, Jennifer ^{[23
]}

Dietrich, Dimo ^{[24
]}

Pop, Oltin T. ^{[25
]}

Flatz, Lukas ^{[25
,26
]}

Dougall, William C. ^{[1
]}

Veillette, Andre ^{[6
,7
,8
]}

Nicholson, Sandra E. ^{[4
,5
]}

Moller, Andreas ^{[3
]}

Johnston, Robert J. ^{[13
]}

Martinet, Ludovic ^{[27
]}

Smyth, Mark J. ^{[1
]}

Bald, Tobias ^{[2
]}

机构：

[1] QIMR Berghofer Med Res Inst, Immunol Canc & Infect Lab, Herston, Qld, Australia

[2] QIMR Berghofer Med Res Inst, Oncol & Cellular Immunol Lab, Herston, Qld, Australia

[3] QIMR Berghofer Med Res Inst, Tumor Microenvironm Lab, Herston, Qld, Australia

[4] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia

[5] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia

[6] Inst Rech Clin Montreal, Lab Mol Oncol, Montreal, PQ, Canada

[7] McGill Univ, Dept Med, Montreal, PQ, Canada

[8] Univ Montreal, Dept Med, Montreal, PQ, Canada

[9] QIMR Berghofer Med Res Inst, Gordon & Jessie Gilmour Leukemia Lab, Herston, Qld, Australia

[10] Univ Bonn, Univ Hosp Bonn, Fac Med, Inst Expt Oncol, Bonn, Germany

[11] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[12] QIMR Berghofer Med Res Inst, Med Genom Lab, Herston, Qld, Australia

[13] Bristol Myers Squibb, Immunooncol Discovery, Redwood City, CA USA

[14] Univ Bonn, Univ Hosp Bonn, Inst Biol Struct, Bonn, Germany

[15] Univ Bonn, Univ Hosp Bonn, Inst Pathol, Bonn, Germany

[16] Univ Queensland Herston, Royal Brisbane & Womens Hosp, Pathol Queensland, Herston, Qld, Australia

[17] Univ Queensland Herston, Royal Brisbane & Womens Hosp, Herston, Qld, Australia

[18] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia

[19] Univ Sydney, Cent Clin Sch, Sydney, NSW, Australia

[20] Royal North Shore Hosp, Sydney, NSW, Australia

[21] Mater Hosp, Sydney, NSW, Australia

[22] Royal Prince Alfred Hosp, Sydney, NSW, Australia

[23] Univ Bonn, Univ Hosp Bonn, Dept Dermatol & Allergy, Bonn, Germany

[24] Univ Bonn, Univ Hosp Bonn, Dept Otolaryngol Head & Neck Surg, Bonn, Germany

[25] Kantonsspital St Gallen, Inst Immunobiol, St Gallen, Switzerland

[26] Kantonsspital St Gallen, Dept Dermatol, St Gallen, Switzerland

[27] INSERM, Canc Res Ctr Toulouse CRCT, UMR 1037, F-31000 Toulouse, France

来源：

IMMUNITY | 2020年 / 53卷 / 04期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 加拿大健康研究院; 瑞士国家科学基金会;

关键词：

LIPID RAFT RECRUITMENT; NATURAL-KILLER; DNAM-1; CD226; IMMUNOLOGICAL SYNAPSE; DENDRITIC CELLS; PVR CD155; KINASE-C; EXPRESSION; PROTEIN; DIFFERENTIATION;

D O I：

10.1016/j.immuni.2020.09.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes antitumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8(+) TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226(hi) TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre-treatment samples from melanoma patients, CD226(+)CD8(+) T cells correlated with improved progression-free survival following ICB. Our findings argue for the development of therapies aimed at maintaining the expression of CD226.

引用

页码：805 / +

页数：34

共 106 条

[1]

Expression of DNAM-1 (CD226) on inflammatory monocytes [J].

Anh Van Vo ;

Takenaka, Eri ;

Shibuya, Akira ;

Shibuya, Kazuko .

MOLECULAR IMMUNOLOGY, 2016, 69 :70-76

[2]

[Anonymous], 2019, gplots: various R programming tools for plotting data

[3]

[Anonymous], 2016, R package

[4]

[Anonymous], 2019, Fundamentals of Data Visualization

[5]

DNAM-1 ligand expression on Ag-stimulated T lymphocytes is mediated by ROS-dependent activation of DNA-damage response: relevance for NK-T cell interaction [J].

Ardolino, Michele ;

Zingoni, Alessandra ;

Cerboni, Cristina ;

Cecere, Francesca ;

Soriani, Alessandra ;

Iannitto, Maria Luisa ;

Santoni, Angela .

BLOOD, 2011, 117 (18) :4778-4786

[6]

Ashhurst T.M., 2017, TSNEPLOTS R SCRIPT

[7]

Costimulatory and Coinhibitory Receptor Pathways in Infectious Disease [J].

Attanasio, John ;

Wherry, E. John .

IMMUNITY, 2016, 44 (05) :1052-1068

[8]

Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma [J].

Bald, Tobias ;

Quast, Thomas ;

Landsberg, Jennifer ;

Rogava, Meri ;

Glodde, Nicole ;

Lopez-Ramos, Dorys ;

Kohlmeyer, Judith ;

Riesenberg, Stefanie ;

van den Boorn-Konijnenberg, Debby ;

Hoemig-Hoelzel, Cornelia ;

Reuten, Raphael ;

Schadow, Benjamin ;

Weighardt, Heike ;

Wenzel, Daniela ;

Helfrich, Iris ;

Schadendorf, Dirk ;

Bloch, Wilhelm ;

Bianchi, Marco E. ;

Lugassy, Claire ;

Barnhill, Raymond L. ;

Koch, Manuel ;

Fleischmann, Bernd K. ;

Foerster, Irmgard ;

Kastenmueller, Wolfgang ;

Kolanus, Waldemar ;

Hoelzel, Michael ;

Gaffal, Evelyn ;

Tueting, Thomas .

NATURE, 2014, 507 (7490) :109-+

[9]

Baptiste Auguie A.A, 2017, gridExtra: Miscellaneous Functions for "Grid" Graphics

[10]

Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells [J].

Bengsch, Bertram ;

Ohtani, Takuya ;

Khan, Omar ;

Setty, Manu ;

Manne, Sasikanth ;

O'Brien, Shaun ;

Gherardini, Pier Federico ;

Herati, Ramin Sedaghat ;

Huang, Alexander C. ;

Chang, Kyong-Mi ;

Newell, Evan W. ;

Bovenschen, Niels ;

Pe'er, Dana ;

Albelda, Steven M. ;

Wherry, E. John .

IMMUNITY, 2018, 48 (05) :1029-+

← 1 2 3 4 5 6 7 8 9 10 →