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Neutralization of TGFβ Improves Tumor Immunity and Reduces Tumor Progression in Ovarian Carcinoma
Ist Teil von
Molecular cancer therapeutics, 2021-03, Vol.20 (3), p.602-611
Ort / Verlag
United States
Erscheinungsjahr
2021
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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;
< 0.001) and improved the CD8:Treg ratio (0.37 vs. 2.5;
= 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;
= 0.002) and increased CD8:Tregs ratio (0.36 vs. 1.49;
= 0.007), while also significantly reducing omental weight (114.9 mg vs. 93.4 mg;
= 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.