Clinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma Journal Article
| Authors: | Valero, C.; Golkaram, M.; Vos, J. L.; Xu, B.; Fitzgerald, C.; Lee, M.; Kaplan, S.; Han, C. Y.; Pei, X.; Sarkar, R.; Boe, L. A.; Pandey, A.; Koh, E. S.; Zuur, C. L.; Solit, D. B.; Pawlowski, T.; Liu, L.; Ho, A. L.; Chowell, D.; Riaz, N.; Chan, T. A.; Morris, L. G. T. |
| Article Title: | Clinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma |
| Abstract: | BACKGROUND. Recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and significant morbidity. While immune checkpoint blockade (ICB) drugs are effective in approximately 20% of patients, the remaining experience limited clinical benefit and are exposed to potential adverse effects and financial costs. Clinically approved biomarkers, such as tumor mutational burden (TMB), have a modest predictive value in HNSCC. METHODS. We analyzed clinical and genomic features, generated using whole-exome sequencing, in 133 ICB-treated patients with R/M HNSCC, of whom 69 had virus-associated and 64 had non-virus-associated tumors. RESULTS. Hierarchical clustering of genomic data revealed 6 molecular subtypes characterized by a wide range of objective response rates and survival after ICB therapy. The prognostic importance of these 6 subtypes was validated in an external cohort. A random forest-based predictive model, using several clinical and genomic features, predicted progression-free survival (PFS), overall survival (OS), and response with greater accuracy than did a model based on TMB alone. Recursive partitioning analysis identified 3 features (systemic inflammatory response index, TMB, and smoking signature) that classified patients into risk groups with accurate discrimination of PFS and OS. CONCLUSION. These findings shed light on the immunogenomic characteristics of HNSCC tumors that drive differential responses to ICB and identify a clinical-genomic classifier that outperformed the current clinically approved biomarker of TMB. This validated predictive tool may help with clinical risk stratification in patients with R/M HNSCC for whom ICB is being considered. © 2023 Valero et al. |
| Keywords: | genetics; mutation; tumor marker; head and neck neoplasms; genomics; head and neck tumor; head and neck squamous cell carcinoma; immune checkpoint inhibitor; humans; human; immune checkpoint inhibitors; biomarkers, tumor; squamous cell carcinoma of head and neck |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 133 |
| Issue: | 19 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2023-10-02 |
| Start Page: | e169823 |
| Language: | English |
| DOI: | 10.1172/jci169823 |
| PUBMED: | 37561583 |
| PROVIDER: | scopus |
| PMCID: | PMC10541199 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Luc G. T. Morris -- Source: Scopus |
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