OncoImmunology (Dec 2022)

Immunomodulation via FGFR inhibition augments FGFR1 targeting T-cell based antitumor immunotherapy for head and neck squamous cell carcinoma

  • Michihisa Kono,
  • Hiroki Komatsuda,
  • Hidekiyo Yamaki,
  • Takumi Kumai,
  • Ryusuke Hayashi,
  • Risa Wakisaka,
  • Toshihiro Nagato,
  • Takayuki Ohkuri,
  • Akemi Kosaka,
  • Kenzo Ohara,
  • Kan Kishibe,
  • Miki Takahara,
  • Akihiro Katada,
  • Tatsuya Hayashi,
  • Hiroya Kobayashi,
  • Yasuaki Harabuchi

DOI
https://doi.org/10.1080/2162402X.2021.2021619
Journal volume & issue
Vol. 11, no. 1

Abstract

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Fibroblast growth factor receptor 1 (FGFR1) is overexpressed in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Being associated with poor prognosis, FGFR1 is a potential therapeutic target for aggressive tumors. T cell-based cancer immunotherapy has played a central role in novel cancer treatments. However, the potential of antitumor immunotherapy targeting FGFR1 has not been investigated. Here, we showed that FGFR-tyrosine kinase inhibitors (TKIs) augmented antitumor effects of immune checkpoint inhibitors in an HNSCC mouse model and upregulated tumoral MHC class I and MHC class II expression in vivo and in vitro. This upregulation was associated with the mitogen-activated protein kinase signaling pathway, which is a crucial pathway for cancer development through FGFR signaling. Moreover, we identified an FGFR1-derived peptide epitope (FGFR1305-319) that could elicit antigen-reactive and multiple HLA-restricted CD4+ T cell responses. These T cells showed direct cytotoxicity against tumor cells that expressed FGFR1. Notably, FGFR-TKIs augmented antitumor effects of FGFR1-reactive T cells against human HNSCC cells. These results indicate that the combination of FGFR-TKIs with immunotherapy, such as an FGFR1-targeting peptide vaccine or immune checkpoint inhibitor, could be a novel and robust immunologic approach for treating patients with FGFR1-expressing cancer cells.

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