Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma.
Cell Rep Med
; 2(10): 100411, 2021 10 19.
Article
en En
| MEDLINE
| ID: mdl-34755131
ABSTRACT
Neoadjuvant PD-1 blockade may be efficacious in some individuals with high-risk, resectable oral cavity head and neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 individuals displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, or JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T cell clones. A high ratio of regulatory T to T helper 17 cells in pretreatment blood predicts low T cell receptor repertoire diversity in pretreatment blood, a low cytolytic T cell signature in pretreatment tumors, and innate resistance. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for individuals with resectable head and neck cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_mouth_oropharynx_cancers
Asunto principal:
Neoplasias de la Boca
/
Carcinoma de Células Escamosas
/
Receptor 3 de Factores de Crecimiento Endotelial Vascular
/
Receptor de Muerte Celular Programada 1
/
Nivolumab
/
Recurrencia Local de Neoplasia
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Rep Med
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos