Tumor-derived TGF-β and prostaglandin E2 attenuate anti-tumor immune responses in head and neck squamous cell carcinoma treated with EGFR inhibitor

Takumi Kumai, Kensuke Oikawa, Naoko Aoki, Shoji Kimura, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background: EGFR-targeted therapy is an attractive option for head and neck squamous cell carcinoma patients. We have recently reported the use of EGFR inhibitors as an adjunct treatment to enhance HLA-DR expression in tumor cells to improve cancer immunotherapy. Nevertheless, we observed that EGFR inhibitors resulted in decreased anti-tumor responses, regardless of upregulation of HLA-DR expression on the tumor cell. In this study, we specifically investigated the mechanisms by which EGFR inhibition modulated anti-tumor responses.Methods: An EGFR inhibitor erlotinib was used to assess the modulation of anti-tumor responses by tumor antigen-specific helper T cells. We then examined whether administration of the EGFR inhibitor altered tumor cytokine profiles and expression of immune-related molecules on tumor cells.Results: Despite the augmented HLA-DR expression on a gingival cancer cell line by EGFR inhibition, anti-tumor responses of EGFR reactive helper T cell clones against tumor cells were decreased. EGFR inhibition did not change the expression of CD80, CD86, or PD-L1 on the tumor cells. Conversely, production of transforming growth factor beta (TGF-β) and prostaglandin E2 was increased by EGFR inhibition, indicating that these immunosuppressive molecules were involved in diminishing tumor recognition by T cells. Significantly, attenuation of HTL responses against tumors after EGFR inhibition was reversed by the addition of anti-TGF-β antibody or COX2 inhibitors.Conclusions: Targeting TGF-β and prostaglandin E2 may allow for improved outcomes for cancer patients treated with combination immunotherapy and EGFR inhibitors.

Original languageEnglish (US)
Article number265
JournalJournal of Translational Medicine
Issue number1
StatePublished - Sep 21 2014
Externally publishedYes


  • COX-2
  • EGFR
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Tumor-derived TGF-β and prostaglandin E2 attenuate anti-tumor immune responses in head and neck squamous cell carcinoma treated with EGFR inhibitor'. Together they form a unique fingerprint.

Cite this