Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma

• Published in: Frontiers in immunology 2024-07, Vol.15, p.1390873
• Main Authors: Tsujikawa, Takahiro, Ohno, Kazuchika, Morita, Kei-Ichi, Saburi, Sumiyo, Mitsuda, Junichi, Yoshimura, Kanako, Kimura, Alisa, Morimoto, Hiroki, Ogi, Hiroshi, Shibata, Saya, Akashi, Takumi, Kurata, Morito, Imoto, Issei, Shimizu, Yasushi, Kano, Satoshi, Watanabe, Akihito, Yamazaki, Tomoko, Asada, Yukinori, Hayashi, Ryuichi, Saito, Yuki, Ozawa, Hiroyuki, Tsukahara, Kiyoaki, Oridate, Nobuhiko, Sano, Daisuke, Horii, Arata, Ueki, Yushi, Maruo, Takashi, Mukoyama, Nobuaki, Hanai, Nobuhiro, Fukusumi, Takahito, Iwai, Hiroshi, Fujisawa, Takuo, Fujii, Takashi, Nibu, Ken-Ichi, Iwae, Shigemichi, Ueda, Tsutomu, Chikuie, Nobuyuki, Yasumatsu, Ryuji, Matsuo, Mioko, Umeno, Hirohito, Ono, Takeharu, Masuda, Muneyuki, Toh, Satoshi, Itoh, Kyoko, Hirano, Shigeru, Asakage, Takahiro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - genetics; biomarker; Biomarkers, Tumor - genetics; Female; Genomics - methods; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - immunology; head and neck squamous cell carcinoma; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; immune profile; Immunology; Male; Middle Aged; Mutation; nivolumab; Nivolumab - adverse effects; Nivolumab - therapeutic use; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - immunology; Treatment Outcome; Tumor Microenvironment - immunology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1390873

In 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. The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing. Of 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, mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including , , and mutations, had lower CPS, higher smoking index, and were associated with poor responses. Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.