{Reference Type}: Journal Article
{Title}: Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma.
{Author}: Tsujikawa T;Ohno K;Morita KI;Saburi S;Mitsuda J;Yoshimura K;Kimura A;Morimoto H;Ogi H;Shibata S;Akashi T;Kurata M;Imoto I;Shimizu Y;Kano S;Watanabe A;Yamazaki T;Asada Y;Hayashi R;Saito Y;Ozawa H;Tsukahara K;Oridate N;Sano D;Horii A;Ueki Y;Maruo T;Mukoyama N;Hanai N;Fukusumi T;Iwai H;Fujisawa T;Fujii T;Nibu KI;Iwae S;Ueda T;Chikuie N;Yasumatsu R;Matsuo M;Umeno H;Ono T;Masuda M;Toh S;Itoh K;Hirano S;Asakage T;
{Journal}: Front Immunol
{Volume}: 15
{Issue}: 0
{Year}: 2024
{Factor}: 8.786
{DOI}: 10.3389/fimmu.2024.1390873
{Abstract}: <B>UNASSIGNED: </B>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.<BR><B>UNASSIGNED: </B>The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing.<BR><B>UNASSIGNED: </B>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, 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.<BR><B>UNASSIGNED: </B>Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.