Blockade of trans PD-L1 interaction with CD80 augments antitumor immunity

被引：20

作者：

Zhang, Yuankun ^{[1
,2
,3
]}

Song, Qingxiao ^{[2
,3
,4
,5
]}

Cassady, Kaniel ^{[2
,6
,9
]}

Lee, Michael ^{[2
,6
]}

Tang, Haidong ^{[7
,10
]}

Zheng, Moqian ^{[2
,3
]}

Wang, Bixin ^{[2
,3
,4
,5
]}

Schones, Dustin E. ^{[2
]}

Fu, Yang-Xin ^{[7
,11
]}

Riggs, Arthur D. ^{[2
]}

Martin, Paul J. ^{[8
]}

Feng, Ru ^{[1
]}

Zeng, Defu ^{[2
,3
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Hematol, Guangzhou 510515, Peoples R China

[2] City Hope Med Ctr, Arthur Riggs Diabet & Metab Res Inst, Duarte, CA 91010 USA

[3] City Hope Natl Med Ctr, Hematol Malignancies & Stem Cell Transplantat Inst, Duarte, CA 91010 USA

[4] Fujian Med Univ, Fujian Inst Hematol, Ctr Translat Hematol, Fuzhou 350001, Peoples R China

[5] Fujian Med Univ, Union Hosp, Fuzhou 350001, Peoples R China

[6] City Hope Natl Med Ctr, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA

[7] Univ Texas Southwestern Med Ctr, Dept Pathol, Dallas, TX 75390 USA

[8] Fred Hutchinson Canc Ctr, Seattle, WA 98109 USA

[9] Dept Hematol & Translat Sci, Regeneron Pharmaceut, Tarrytown, NY 10591 USA

[10] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China

[11] Tsinghua Univ, Sch Med, Dept Basic Med Sci, Beijing 100084, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2023年 / 120卷 / 16期

关键词：

PD-L1; CD80; PD-L1 interaction with CD80; CD8+T cells; tumor immunity; NITRIC-OXIDE SYNTHASE; T-CELL-ACTIVATION; CHECKPOINT BLOCKADE; MYELOID CELLS; TUMOR-CELLS; B7; FAMILY; EXPRESSION; RECEPTOR; B7-H1; INDUCTION;

D O I：

10.1073/pnas.2205085120

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

PD-L1 has two receptors: PD-1 and CD80. Previous reports assumed that PD-L1 and CD80 interacted in trans, but recent reports showed that only cis PD-L1/CD80 interactions existed, and prevention of cis PD-L1/CD80 interactions on antigen-presenting cells (APCs) reduced antitumor immunity via augmenting PD-L1/PD-1 and CD80/ CTLA4 interactions between T and APCs. Here, using tumor-bearing mice capable of cis and trans or trans only PD-L1/CD80 interactions, we show that trans PD-L1/CD80 interactions do exist between tumor and T cells, and the effects of trans PD-L1/CD80 interactions require tumor cell expression of MHC-I and T cell expression of CD28. The blockade of PD-L1/CD80 interactions in mice with both cis and trans interactions or with only trans interactions augments antitumor immunity by expanding IFN-& gamma;-producing CD8+ T cells and IFN-& gamma;-dependent NOS2-expressing tumor-associated macrophages. Our studies indicate that although cis and trans PD-L1/CD80 interactions may have opposite effects on antitumor immunity, the net effect of blocking PD-L1/CD80 interactions in vivo augments CD8+ T cell-mediated antitumor immunity.

引用

页数：11

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