Pivotal antitumor role of the immune checkpoint molecule B7-H1 in pancreatic cancer

被引：3

作者：

Bazhin, Alexandr, V ^{[1
]}

von Ahn, Katharina ^{[1
]}

Fritz, Jasmin ^{[1
]}

Bunge, Henriette ^{[1
]}

Maier, Caroline ^{[1
]}

Isayev, Orkhan ^{[2
]}

Neff, Florian ^{[3
,4
]}

Siveke, Jens T. ^{[3
,4
,5
]}

Karakhanova, Svetlana ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany

[2] Azerbaijan Med Univ, Dept Cytol Embryol & Histol, Baku, Azerbaijan

[3] German Canc Res Ctr, Div Solid Tumor Translat Oncol, Heidelberg, Germany

[4] German Canc Consortium DKTK, Partner Site Univ Hosp Essen, Heidelberg, Germany

[5] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Bridge Inst Expt Tumor Therapy, Essen, Germany

来源：

ONCOIMMUNOLOGY | 2022年 / 11卷 / 01期

关键词：

B7-H1 (PD-L1); B7-H1; knockout; immune checkpoint molecules; immunosuppression; cancer immunotherapy; pancreatic cancer; TUMOR-ASSOCIATED MACROPHAGES; SUPPRESSOR-CELLS; B7; FAMILY; CLINICAL-SIGNIFICANCE; IMPROVES SURVIVAL; PD-L1; EXPRESSION; T-CELLS; BLOCKADE; MODEL; INDUCTION;

D O I：

10.1080/2162402X.2022.2043037

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Immune checkpoint molecule B7-H1 plays a decisive immune regulatory role in different pathologies including cancer, and manipulation of B7-H1 expression became an attractive approach in cancer immunotherapy. Pancreatic cancer (PDAC) is characterized by pronounced immunosuppressive environment and B7-H1 expression correlates with PDAC prognosis. However, the first attempts to diminish B7-H1 expression in patients were not so successful. This points the complicity of PDAC immunosuppressive network and requires further examinations. We investigated the effect of B7-H1 deficiency in PDAC. Our results clearly show that partial or complete B7-H1 inhibition in vivo let to reduced tumor volume and improved survival of PDAC-bearing mice. This oncological benefit is due to the abrogation of immunosuppression provided by MDSC, macrophages, DC and Treg, which resulted in simultaneous restoration of anti-tumor immune response, namely improved accumulation and functionality of effector-memory CD4 and CD8 T cells. Our results underline the potential of B7-H1 molecule to control immunosuppressive network in PDAC and provide new issues for further clinical investigations.

引用

页数：14

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