Introduction: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy. Methods: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules. Results: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant (p-value <= 0.05) correlation with alive status was evidenced for sE-selectin at T1. Conclusions: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy.

Genomic and immune approach in platinum refractory HPV-negative head and neck squamous cell carcinoma patients treated with Immunotherapy: a novel combined profile / Mezi, Silvia; Pomati, Giulia; Zizzari, ILARIA GRAZIA; DI FILIPPO, Alessandra; Cerbelli, Bruna; Cirillo, Alessio; Fiscon, Giulia; Amirhassankhani, Sasan; Valentini, Valentino; DE VINCENTIIS, Marco; Corsi, Alessandro; DI GIOIA, Cira Rosaria Tiziana; Tombolini, Vincenzo; DELLA ROCCA, Carlo; Polimeni, Antonella; Nuti, Marianna; Marchetti, Paolo; Botticelli, Andrea. - In: BIOMEDICINES. - ISSN 2227-9059. - 10:11(2022). [10.3390/biomedicines10112732]

Genomic and immune approach in platinum refractory HPV-negative head and neck squamous cell carcinoma patients treated with Immunotherapy: a novel combined profile

Silvia Mezi
Primo
;
Giulia Pomati
Secondo
;
Ilaria Grazia Zizzari;Alessandra Di Filippo;Bruna Cerbelli;Alessio Cirillo;Giulia Fiscon;Valentino Valentini;Marco De Vincentiis;Alessandro Corsi;Cira Di Gioia;Vincenzo Tombolini;Carlo Della Rocca;Antonella Polimeni;Marianna Nuti;Paolo Marchetti
Penultimo
;
Andrea Botticelli
Ultimo
2022

Abstract

Introduction: Only a minority of patients with platinum refractory head and neck squamous cell carcinoma (PR/HNSCC) gain some lasting benefit from immunotherapy. Methods: The combined role of the comprehensive genomic (through the FoundationOne Cdx test) and immune profiles of 10 PR/HNSCC patients treated with the anti-PD-1 nivolumab was evaluated. The immune profiles were studied both at baseline and at the second cycle of immunotherapy, weighing 20 circulating cytokines/chemokines, adhesion molecules, and 14 soluble immune checkpoints dosed through a multiplex assay. A connectivity map was obtained by calculating the Spearman correlation between the expression profiles of circulating molecules. Results: Early progression occurred in five patients, each of them showing TP53 alteration and three of them showing a mutation/loss/amplification of genes involved in the cyclin-dependent kinase pathway. In addition, ERB2 amplification (1 patient), BRCA1 mutation (1 patient), and NOTCH1 genes alteration (3 patients) occurred. Five patients achieved either stable disease or partial response. Four of them carried mutations in PI3K/AKT/PTEN pathways. In the only two patients, with a long response to immunotherapy, the tumor mutational burden (TMB) was high. Moreover, a distinct signature, in terms of network connectivity of the circulating soluble molecules, characterizing responder and non-responder patients, was evidenced. Moreover, a strong negative and statistically significant (p-value <= 0.05) correlation with alive status was evidenced for sE-selectin at T1. Conclusions: Our results highlighted the complexity and heterogeneity of HNSCCs, even though it was in a small cohort. Molecular and immune approaches, combined in a single profile, could represent a promising strategy, in the context of precision immunotherapy.
2022
chemokines; cytokines profile; gene mutation; head and neck cancer; immunotherapy; soluble immune checkpoints
01 Pubblicazione su rivista::01a Articolo in rivista
Genomic and immune approach in platinum refractory HPV-negative head and neck squamous cell carcinoma patients treated with Immunotherapy: a novel combined profile / Mezi, Silvia; Pomati, Giulia; Zizzari, ILARIA GRAZIA; DI FILIPPO, Alessandra; Cerbelli, Bruna; Cirillo, Alessio; Fiscon, Giulia; Amirhassankhani, Sasan; Valentini, Valentino; DE VINCENTIIS, Marco; Corsi, Alessandro; DI GIOIA, Cira Rosaria Tiziana; Tombolini, Vincenzo; DELLA ROCCA, Carlo; Polimeni, Antonella; Nuti, Marianna; Marchetti, Paolo; Botticelli, Andrea. - In: BIOMEDICINES. - ISSN 2227-9059. - 10:11(2022). [10.3390/biomedicines10112732]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1660536
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