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Article: Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8+ T Cells

TitleCo-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8<sup>+</sup> T Cells
Authors
Keywordscombinational blockade of immune checkpoints
Eomes
PD-1
B7S1
T cell exhaustion
tumor immunity
Issue Date2018
Citation
Immunity, 2018, v. 48, n. 4, p. 773-786.e5 How to Cite?
Abstract© 2018 Elsevier Inc. The molecular mechanisms whereby CD8+ T cells become “exhausted” in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation. Here we show increased B7S1 expression on myeloid cells from human hepatocellular carcinoma correlated with CD8+ T cell dysfunction. B7S1 inhibition suppressed development of murine tumors. Putative B7S1 receptor was co-expressed with PD-1 but not T cell immunoglobulin and mucin-domain containing-3 (Tim-3) at an activated state of early tumor-infiltrating CD8+ T cells, and B7S1 promoted T cell exhaustion, possibly through Eomes overexpression. Combinatorial blockade of B7S1 and PD-1 synergistically enhanced anti-tumor immune responses. Collectively, B7S1 initiates dysfunction of tumor-infiltrating CD8+ T cells and may be targeted for cancer immunotherapy. Mechanisms driving T cell exhaustion have not been understood. Li et al. demonstrate that B7S1 on tumor-infiltrating myeloid cells initiates exhaustion of activated CD8+ TILs through upregulating Eomes, thus proposing B7S1 as a promising target to enhance the efficacy of anti-PD-1 therapy.
Persistent Identifierhttp://hdl.handle.net/10722/293080
ISSN
2020 Impact Factor: 31.745
2015 SCImago Journal Rankings: 16.215
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Jing-
dc.contributor.authorLee, Younghee-
dc.contributor.authorLi, Yanjian-
dc.contributor.authorJiang, Yu-
dc.contributor.authorLu, Huiping-
dc.contributor.authorZang, Wenjuan-
dc.contributor.authorZhao, Xiaohong-
dc.contributor.authorLiu, Liguo-
dc.contributor.authorChen, Yang-
dc.contributor.authorTan, Haidong-
dc.contributor.authorYang, Zhiying-
dc.contributor.authorZhang, Michael Q.-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorNi, Ling-
dc.contributor.authorDong, Chen-
dc.date.accessioned2020-11-17T14:57:50Z-
dc.date.available2020-11-17T14:57:50Z-
dc.date.issued2018-
dc.identifier.citationImmunity, 2018, v. 48, n. 4, p. 773-786.e5-
dc.identifier.issn1074-7613-
dc.identifier.urihttp://hdl.handle.net/10722/293080-
dc.description.abstract© 2018 Elsevier Inc. The molecular mechanisms whereby CD8+ T cells become “exhausted” in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation. Here we show increased B7S1 expression on myeloid cells from human hepatocellular carcinoma correlated with CD8+ T cell dysfunction. B7S1 inhibition suppressed development of murine tumors. Putative B7S1 receptor was co-expressed with PD-1 but not T cell immunoglobulin and mucin-domain containing-3 (Tim-3) at an activated state of early tumor-infiltrating CD8+ T cells, and B7S1 promoted T cell exhaustion, possibly through Eomes overexpression. Combinatorial blockade of B7S1 and PD-1 synergistically enhanced anti-tumor immune responses. Collectively, B7S1 initiates dysfunction of tumor-infiltrating CD8+ T cells and may be targeted for cancer immunotherapy. Mechanisms driving T cell exhaustion have not been understood. Li et al. demonstrate that B7S1 on tumor-infiltrating myeloid cells initiates exhaustion of activated CD8+ TILs through upregulating Eomes, thus proposing B7S1 as a promising target to enhance the efficacy of anti-PD-1 therapy.-
dc.languageeng-
dc.relation.ispartofImmunity-
dc.subjectcombinational blockade of immune checkpoints-
dc.subjectEomes-
dc.subjectPD-1-
dc.subjectB7S1-
dc.subjectT cell exhaustion-
dc.subjecttumor immunity-
dc.titleCo-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8<sup>+</sup> T Cells-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.immuni.2018.03.018-
dc.identifier.pmid29625896-
dc.identifier.scopuseid_2-s2.0-85044646402-
dc.identifier.volume48-
dc.identifier.issue4-
dc.identifier.spage773-
dc.identifier.epage786.e5-
dc.identifier.eissn1097-4180-
dc.identifier.isiWOS:000430198900022-
dc.identifier.issnl1074-7613-

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