Immune Checkpoint Blockade Enhances Immune Activity of Therapeutic Lung Cancer Vaccine

被引：2

作者：

Kadam, Pournima ^{[1
]}

Singh, Ram P. ^{[1
]}

Davoodi, Michael ^{[1
]}

Lee, Jay M. ^{[2
,3
]}

John, Maie St. ^{[3
,4
,5
]}

Sharma, Sherven ^{[1
,2
,3
]}

机构：

[1] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Head & Neck Surg, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Head & Neck Canc Program, Los Angeles, CA 90095 USA

来源：

VACCINES | 2020年 / 8卷 / 04期

关键词：

lung cancer; PD-1; CCL21; dendritic cells (DC); T cells; tumor microenvironment (TME); REGULATORY T-CELLS;

D O I：

10.3390/vaccines8040655

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background: Immune checkpoint blockade that downregulates T cell evasion for effective immunity has provided a renewed interest in therapeutic cancer vaccines. Methods: Utilizing murine lung cancer models, we determined: tumor burden, TIL cytolysis, immunohistochemistry, flow cytometry, RNA Sequencing, CD4 T cells, CD8 T cells, CXCL9 chemokine, and CXCL10 chemokine neutralization to evaluate the efficacy of Programmed cell death protein 1 (PD-1) blockade combined with chemokine (C-C motif) ligand 21-dendritic cell tumor antigen (CCL21-DC tumor Ag) vaccine. Results: Anti-PD1 combined with CCL21-DC tumor Ag vaccine eradicated 75% of 12-day established tumors (150 mm(3)) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy. The effect of combined therapy was blocked by CD4, CD8, CXCL9, and CXCL10 neutralizing antibodies. Conclusion: PD-1 blockade therapy plus CCL21-DC tumor Ag vaccine could be beneficial to lung cancer patients.

引用

页码：1 / 9

页数：9

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