Neutralization of TGFβ Improves Tumor Immunity and Reduces Tumor Progression in Ovarian Carcinoma.

Autor:	Roane BM; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama., Meza-Perez S; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama., Katre AA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama., Goldsberry WN; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama., Randall TD; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Comprehensive Cancer Center, University of Alabama at Birmingham, Alabama., Norian LA; Comprehensive Cancer Center, University of Alabama at Birmingham, Alabama.; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama., Birrer MJ; Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas., Arend RC; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama. rarend@uabmc.edu.; Comprehensive Cancer Center, University of Alabama at Birmingham, Alabama.
Jazyk:	angličtina
Zdroj:	Molecular cancer therapeutics [Mol Cancer Ther] 2021 Mar; Vol. 20 (3), pp. 602-611. Date of Electronic Publication: 2020 Dec 15.
DOI:	10.1158/1535-7163.MCT-20-0412
Abstrakt:	The immunosuppressive effects of TGFβ promotes tumor progression and diminishes response to therapy. In this study, we used ID8-p53 -/- tumors as a murine model of high-grade serous ovarian cancer. An mAb targeting all three TGFβ ligands was used to neutralize TGFβ. Ascites and omentum were collected and changes in T-cell response were measured using flow. Treatment with anti-TGFβ therapy every other day following injection of tumor cells resulted in decreased ascites volume (4.1 mL vs. 0.7 mL; P < 0.001) and improved the CD8:Treg ratio (0.37 vs. 2.5; P = 0.02) compared with untreated mice. A single dose of therapy prior to tumor challenge resulted in a similar reduction of ascites volume (2.7 vs. 0.67 mL; P = 0.002) and increased CD8:Tregs ratio (0.36 vs. 1.49; P = 0.007), while also significantly reducing omental weight (114.9 mg vs. 93.4 mg; P = 0.017). Beginning treatment before inoculation with tumor cells and continuing for 6 weeks, we observe similar changes and prolonged overall survival (median 70 days vs. 57.5 days). TGFβ neutralization results in favorable changes to the T-cell response within the tumor microenvironment, leading to decreased tumor progression in ovarian cancer. The utilization of anti-TGFβ therapy may be an option for management in patients with ovarian cancer to improve clinical outcomes and warrants further investigation. (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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