Blockade of PD-1 effectively inhibits in vivo malignant transformation of oral mucosa

Yichen Chen, Qiusheng Li, Xinye Li, Da Ma, Juan Fang, Liqun Luo, Xiangqi Liu, Xi Wang, Vivian Wai Yan Lui, Juan Xia, Bin Cheng, Zhi Wang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in “activated” T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.

Original languageEnglish (US)
Article numbere1388484
JournalOncoImmunology
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2018
Externally publishedYes

Keywords

  • immunotherapy
  • pre-cancerous lesions
  • programmed death receptor 1
  • squamous cell carcinomas

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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