Journal
CELL PROLIFERATION
Volume 55, Issue 4, Pages -Publisher
WILEY
DOI: 10.1111/cpr.13207
Keywords
cytokine secretion; inhibitory receptors; oral carcinogenesis; PD-1 blockade; regulatory T cell (Treg); T cell exhaustion
Categories
Funding
- National Natural Science of Foundation of PR China [81972532, 81772896, 82101017]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515110741]
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T-cell dysfunction was established at the early premalignant phase of oral carcinogenesis; PD-1 blockade at the early premalignant phase can effectively reverse T-cell exhaustion features and then prevent carcinogenesis progression.
Objectives This study aimed to clarify the dynamic changes of exhaustion features in T cells during oral carcinogenesis. Materials and Methods Mice were randomly divided into 4NQO group and control group. The exhaustion features of CD4(+) and CD8(+) T cells of both groups were detected by flow cytometry. Furthermore, multiplex immunohistochemistry was used to evaluate the expression of inhibitory receptors in human normal, dysplastic, and carcinogenesis tissues. Finally, anti-PD-1 antibody treatment was performed at the early premalignant phase of oral carcinogenesis. Results The proportion of naive T cells in 4NQO group was lower than those in control group, while the proportion of effector memory T cells was higher in 4NQO group. The expression of inhibitory receptors on CD4(+) and CD8(+) T cells increased gradually during carcinogenesis. In contrast, the secretion of cytokines by CD4(+) and CD8(+) T cells decreased gradually with the progression stage. Strikingly, those changes occurred before the onset of oral carcinogenesis. The expression of inhibitory receptors on T cells increased gradually as the human tissues progressed from normal, dysplasia to carcinoma. Interestingly, PD-1 blockade at the early premalignant phase could reverse carcinogenesis progression by restoring T cell function. Conclusions T-cell dysfunction was established at the early premalignant phase of oral carcinogenesis; PD-1 blockade at the early premalignant phase can effectively reverse T-cell exhaustion features and then prevent carcinogenesis progression.
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