Frontiers in Immunology (Jul 2024)
Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma
- Takahiro Tsujikawa,
- Takahiro Tsujikawa,
- Kazuchika Ohno,
- Kei-ichi Morita,
- Sumiyo Saburi,
- Junichi Mitsuda,
- Kanako Yoshimura,
- Alisa Kimura,
- Hiroki Morimoto,
- Hiroshi Ogi,
- Hiroshi Ogi,
- Saya Shibata,
- Takumi Akashi,
- Morito Kurata,
- Issei Imoto,
- Yasushi Shimizu,
- Satoshi Kano,
- Akihito Watanabe,
- Tomoko Yamazaki,
- Yukinori Asada,
- Ryuichi Hayashi,
- Yuki Saito,
- Hiroyuki Ozawa,
- Kiyoaki Tsukahara,
- Nobuhiko Oridate,
- Daisuke Sano,
- Arata Horii,
- Yushi Ueki,
- Takashi Maruo,
- Nobuaki Mukoyama,
- Nobuhiro Hanai,
- Takahito Fukusumi,
- Hiroshi Iwai,
- Takuo Fujisawa,
- Takashi Fujii,
- Ken-ichi Nibu,
- Shigemichi Iwae,
- Tsutomu Ueda,
- Nobuyuki Chikuie,
- Ryuji Yasumatsu,
- Mioko Matsuo,
- Hirohito Umeno,
- Takeharu Ono,
- Muneyuki Masuda,
- Satoshi Toh,
- Kyoko Itoh,
- Shigeru Hirano,
- Takahiro Asakage
Affiliations
- Takahiro Tsujikawa
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Takahiro Tsujikawa
- Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR, United States
- Kazuchika Ohno
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
- Kei-ichi Morita
- Department of Maxillofacial Surgery, Tokyo Medical and Dental University, Tokyo, Japan
- Sumiyo Saburi
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Junichi Mitsuda
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Kanako Yoshimura
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Alisa Kimura
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Hiroki Morimoto
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Hiroshi Ogi
- Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Hiroshi Ogi
- SCREEN Holdings, Kyoto, Japan
- Saya Shibata
- SCREEN Holdings, Kyoto, Japan
- Takumi Akashi
- Department of Diagnostic Pathology, Tokyo Medical and Dental University, Tokyo, Japan
- Morito Kurata
- Department of Comprehensive Pathology, Tokyo Medical and Dental University, Tokyo, Japan
- Issei Imoto
- Aichi Cancer Center Research Institute, Nagoya, Japan
- Yasushi Shimizu
- 0Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Satoshi Kano
- 1Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Akihito Watanabe
- 2Department of Otolaryngology- Head and Neck Surgery, Keiyukai Sapporo Hospital, Sapporo, Japan
- Tomoko Yamazaki
- 3Department Head and Neck Oncology Division, Saitama Medical University International Medical Center, Hidaka, Japan
- Yukinori Asada
- 4Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan
- Ryuichi Hayashi
- 5Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan
- Yuki Saito
- 6Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Hiroyuki Ozawa
- 7Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan
- Kiyoaki Tsukahara
- 8Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan
- Nobuhiko Oridate
- 9Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan
- Daisuke Sano
- 9Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan
- Arata Horii
- 0Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Yushi Ueki
- 0Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
- Takashi Maruo
- 1Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Nobuaki Mukoyama
- 1Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Nobuhiro Hanai
- 2Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
- Takahito Fukusumi
- 3Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
- Hiroshi Iwai
- 4Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University Hospital, Osaka, Japan
- Takuo Fujisawa
- 4Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University Hospital, Osaka, Japan
- Takashi Fujii
- 5Department of Head and Neck Surgery, Osaka International Cancer Institute, Osaka, Japan
- Ken-ichi Nibu
- 6Department of Otolaryngology–Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
- Shigemichi Iwae
- 7Department of Head and Neck Surgery, Hyogo Cancer Center, Akashi, Japan
- Tsutomu Ueda
- 8Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital, Hiroshima, Japan
- Nobuyuki Chikuie
- 8Department of Otolaryngology and Head and Neck Surgery, Hiroshima University Hospital, Hiroshima, Japan
- Ryuji Yasumatsu
- 9Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
- Mioko Matsuo
- 0Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Hirohito Umeno
- 1Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
- Takeharu Ono
- 1Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
- Muneyuki Masuda
- 2Department of Head and Neck Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
- Satoshi Toh
- 2Department of Head and Neck Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
- Kyoko Itoh
- Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Shigeru Hirano
- Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Takahiro Asakage
- Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan
- DOI
- https://doi.org/10.3389/fimmu.2024.1390873
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundIn view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC. MethodsThe study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing.ResultsOf 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses. ConclusionNivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.
Keywords
