Abstract 4709: EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells in vitro.

Abstract

Abstract Despite immunotherapy is a promising approach for cancer treatment, there are many obstacles remain to be overcome. The characteristics of tumor evasion of immune surveillance are produced by decreased expression of immune molecules and secretion of immunoregulatory cytokines. To break these tumor microenvironment which act as suppressor of antitumor immunology, we evaluated the value of EGFR inhibitors as immune-modulators. Following two days EGFR tyrosine kinase inhibitor treatment, expression of HLA-DR molecule of head and neck squamous cancer (HNSCC) cell lines were increased, meanwhile EGFR blocking antibody treatment augmented HLA-DR expression. Furthermore, EGFR inhibitors decreased spontaneous secretion of IL-8 and TGF-β from HNSCC cell lines. To confirm the immune supporting activity of EGFR inhibitors, tumor antigen specific CD4 helper T lymphocyte (HTL) responses to EGFR-expressing tumor were investigated. We identified novel EGFR HTL epitope using MHC class II binding algorithms. The candidate EGFR peptide elicited HTL responses against EGFR-expressing HNSCC in vitro. The EGFR peptide shares high homology to HER2, HER-3 and c-Met, so that these were able to stimulate EGFR peptide reactive HTLs responses in a HLA-DR restricted manner indicating that the EGFR peptide serves a universal tumor-associated peptide in HER family and c-Met. Finally, we evaluated EGFR reactive HTL responses against HNSCC cell lines treated with EGFR inhibitors. As a result, EGFR inhibitors drastically increased HTL IFN-γ production and cytotoxic response. Since HER family and c-MET have been considered as targets of alternative pathway of EGFR inhibition, therapeutic strategy combining EGFR inhibitors with novel HTL epitope identified in this study might be attractive option for antitumor immunotherapy. Citation Format: Takumi Kumai, Yasuaki Harabuchi, Hiroya Kobayashi. EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4709. doi:10.1158/1538-7445.AM2013-4709