PD-1 inhibitors dependent CD8+ T cells inhibit mouse colon cancer cell metastasis.

Abstract

BackgroundColon 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.PurposeThe objective of this study was to investigate the function of PD-1 inhibitor on the metastasisi of mouse colon cancer cells.Patients and methodsIn 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). CD44high CD62Llow 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).ResultsWe 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 CD44high CD62Llow 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.ConclusionThese results suggest that PD-1 inhibitors rely on CD8+ T cells to exert anti-tumor immunity in colon cancer.