PD-1 inhibitors dependent CD8 + T cells inhibit mouse colon cancer cell metastasis.
| Autor: | Gao CE; The First Affiliated Hospital of Kunming Medical University, Department of Medical Oncology, Kunming, Yunnan 650031, People's Republic of China.; Yunnan Cancer Hospital & the Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Department of Medical Oncology, Kunming, Yunnan 650018, People's Republic of China., Zhang M; Yunnan Cancer Hospital & the Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Cancer Research Institute, Kunming, Yunnan 650018, People's Republic of China., Song Q; Yunnan Cancer Hospital & the Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Department of Radiation Oncology, Kunming, Yunnan 650018, People's Republic of China., Dong J; Yunnan Cancer Hospital & the Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center, Department of Medical Oncology, Kunming, Yunnan 650018, People's Republic of China. |
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| Jazyk: | angličtina |
| Zdroj: | OncoTargets and therapy [Onco Targets Ther] 2019 Aug 28; Vol. 12, pp. 6961-6971. Date of Electronic Publication: 2019 Aug 28 (Print Publication: 2019). |
| DOI: | 10.2147/OTT.S202941 |
| Abstrakt: | Background: Colon cancer is a common digestive tract malignancy which ranks as the third leading cause of cancer death worldwide. A current focus of anti-cancer research is harnessing the patient's own immune system for therapy. Programmed cell death protein 1 (PD-1), an immune suppressor, is upregulated in various activated immune cells, such as T cells, and in viral infections and tumors. Purpose: The objective of this study was to investigate the function of PD-1 inhibitor on the metastasisi of mouse colon cancer cells. Patients and Methods: In the present study, we established an in situ colon cancer mouse model using the CT26 cell line. Hematoxylin-eosin (HE) staining was performed to detect colon cancer cell metastasis. The levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12) in serum and mesenteric lymph nodes (MLNs) were detected by Enzyme-linked immunosorbent assay (ELISA). CD44 high CD62L low memory T cells, CD4 + FoxP3 + regulatory T cells, and IFN-γ and TNF-α levels in MLNs and spleen were detected by flow cytometry (FCM). Results: We found that anti-PD-1 therapy inhibited colon cancer cells metastasis to the small intestine, liver, and lung, and lengthened the survival time of mice. However, the depletion of CD8 suppressed the activity of anti-PD-1 antibodies. In response to anti-PD-1 immunotherapy, the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12) in serum and mesenteric lymph nodes (MLNs) were significantly increased, while IL-6, IL-17, and transforming growth factor-β (TGF-β) were decreased. CD8 depletion had the opposite effect. In addition, anti-PD-1 treatment significantly increased CD44 high CD62L low memory T cells, decreased CD4 + FoxP3 + regulatory T cells, and increased IFN-γ and TNF-α levels in MLNs and spleen. Furthermore, anti-PD-1 treatment cannot exert these roles when CD8 is depleted. Conclusion: These results suggest that PD-1 inhibitors rely on CD8+ T cells to exert anti-tumor immunity in colon cancer. Competing Interests: The authors report no conflicts of interest in this work. (© 2019 Gao et al.) |
| Databáze: | MEDLINE |
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