期刊
CANCERS
卷 9, 期 6, 页码 -出版社
MDPI AG
DOI: 10.3390/cancers9060062
关键词
cytokines; head and neck cancer; head and neck squamous cell carcinoma; immunotherapy; PD-1; premalignant oral lesions; T cell
类别
资金
- Merck Investigator-Initiated Studies Program [52353]
- Clinical Sciences Research and Development Program of the Department of Veterans Affairs [I01-CX000851]
A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN-gamma and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-, whose secretion increased late in the treatment period. This delayed secretion of IFN- coincided with an increase in CD4(+) lymph node cells expressing IFN-gamma Lymph node cells of PD-1 antibody-treated mice reacted to a challenge with lysates of lesions or cancer by early production of IFN-gamma, but this rapidly subsided. There also was increased production IL-17 and tumor necrosis factor (TNF)-alpha in response to the challenge, but the response was greatest by cells of control lesion-bearing mice. Clinical assessment showed an early but transient, stabilization of disease in mice treated with PD-1 antibody. These results show an early beneficial, but time-limited, response to PD-1 antibody treatment, which then fails with continued lesion progression.
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