Syndecan-1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD1 checkpoint immunotherapy

被引：0

作者：

Liu, Yun ^{[1
]}

Xu, Chen ^{[1
]}

Zhang, Li ^{[1
]}

Xu, Guiqin ^{[1
]}

Yang, Zhaojuan ^{[1
]}

Xiang, Lvzhu ^{[1
]}

Jiao, Kun ^{[1
]}

Chen, Zehong ^{[1
]}

Zhang, Xiaoren ^{[2
]}

Liu, Yongzhong ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, State Key Lab Syst Med Canc,Sch Med, Shanghai 200032, Peoples R China

[2] Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou, Peoples R China

来源：

SCIENCE ADVANCES | 2024年 / 10卷 / 37期

基金：

中国国家自然科学基金;

关键词：

CTLA-4; BLOCKADE; RESISTANCE; CELLS; THERAPY; GENE; BIOGENESIS; SYNTENIN; SUBSETS; MYELOMA; CD138;

D O I：

10.1126/sciadv.adi7764

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：

Tumor cell-originated events prevent efficient antitumor immune response and limit the application of anti-PD1 checkpoint immunotherapy. We show that syndecan-1 (SDC1) has a critical role in the regulation of T cell-mediated control of tumor growth. SDC1 inhibition increases the permeation of CD8(+) T cells into tumors and triggers CD8(+) T cell-mediated control of tumor growth, accompanied by increased proportions of progenitor-exhausted and effector-like CD8+ T cells. SDC1 deficiency alters multiple signaling events in tumor cells, including enhanced IFN-gamma-STAT1 signaling, and augments antigen presentation and sensitivity to T cell-mediated cytotoxicity. Combinatory inhibition of SDC1 markedly potentiates the therapeutic effects of anti-PD1 in inhibiting tumor growth. Consistently, the findings are supported by the data from human tumors showing that SDC1 expression negatively correlates with T cell presence in tumor tissues and the response to immune checkpoint blockade therapy. Our findings suggest that SDC1 inhibits antitumor immunity, and that targeting SDC1 may promote anti-PD1 response for cancer treatment.

引用

页数：15