Reference - Detail
|Author||Kumai T, Oikawa K, Aoki N, Kimura S, Harabuchi Y, Celis E, Kobayashi H.|
|Title||Tumor-derived TGF-β and prostaglandin E2 attenuate anti-tumor immune responses in head and neck squamous cell carcinoma treated with EGFR inhibitor.|
|Journal||J Transl Med|
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.
|MeSH||CD4-Positive T-Lymphocytes / immunology Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / immunology* Cell Line, Tumor Dinoprostone / physiology* ErbB Receptors / antagonists & inhibitors* Erlotinib Hydrochloride / pharmacology Erlotinib Hydrochloride / therapeutic use* Head and Neck Neoplasms / drug therapy Head and Neck Neoplasms / immunology* Humans Transforming Growth Factor beta / physiology*|
|WOS Category||MEDICINE, RESEARCH & EXPERIMENTAL|
|Human and Animal Cells|