PD‑L1 promotes head and neck squamous cell carcinoma cell growth through mTOR signaling

Oncol Rep. 2019 May;41(5):2833-2843. doi: 10.3892/or.2019.7053. Epub 2019 Mar 7.

Abstract

Programmed death‑ligand 1 (PD‑L1), an immune co‑stimulatory molecule, is expressed on various cancer cells and the surface of immune cells. Its overexpression on tumor cells suppresses the immune response to promote tumor cell immune escape. The present study demonstrated that PD‑L1 was critical in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. Immunohistochemical analysis of HNSCC tissue microarrays revealed that PD‑L1 was overexpressed in tumor tissue, and its expression increased as tumor malignancy progressed (from grade I to IV). Subsequently, the expression of PD‑L1 was knocked down or overexpressed in the HNSCC cell lines Cal‑27 and Fadu. It was demonstrated that PD‑L1 significantly induced HNSCC cell proliferation and colony forming ability. Cell proliferation was also promoted in Cal‑27 cell xenograft BALB/c nude mice. In addition, it was determined by western blotting that the PD‑L1‑mediated increase in HNSCC cell proliferation may have been associated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, mTOR inhibitor (rapamycin) prevented the increase in proliferation. Based on these results, it was concluded that PD‑L1 promoted cell proliferation of HNSCC cells through mTOR signaling, and blocking PD‑L1 may be conducive in HNSCC therapy.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / drug effects
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*
  • Tissue Array Analysis
  • Xenograft Model Antitumor Assays

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus