Genomic and Immune Approach in Platinum Refractory HPV-Negative Head and Neck Squamous Cell Carcinoma Patients Treated with Immunotherapy: A Novel Combined Profile

被引:3
作者
Mezi, Silvia [1 ]
Pomati, Giulia [2 ]
Zizzari, Ilaria Grazia [3 ]
Di Filippo, Alessandra [3 ]
Cerbelli, Bruna [1 ]
Cirillo, Alessio [1 ]
Fiscon, Giulia [4 ]
Amirhassankhani, Sasan [5 ]
Valentini, Valentino [6 ]
De Vincentiis, Marco [6 ]
Corsi, Alessandro [2 ]
Di Gioia, Cira [1 ]
Tombolini, Vincenzo [1 ]
Della Rocca, Carlo [7 ]
Polimeni, Antonella [6 ]
Nuti, Marianna [3 ]
Marchetti, Paolo [8 ]
Botticelli, Andrea [1 ]
机构
[1] Sapienza Univ Rome, Dept Radiol Oncol & Pathol Sci, I-00161 Rome, Italy
[2] Sapienza Univ Rome, Dept Mol Med, I-00161 Rome, Italy
[3] Sapienza Univ Rome, Fac Med & Dent, Dept Expt Med, I-00161 Rome, Italy
[4] Sapienza Univ Rome, Dept Comp Control & Management Engn Antonio Ruber, I-00185 Rome, Italy
[5] Univ Bologna, Dept Urol, S Orsola Malpighi Hosp, Via Palagi 9, I-40138 Bologna, Italy
[6] Sapienza Univ Rome, Dept Oral & Maxillo Facial Sci, I-00161 Rome, Italy
[7] Sapienza Univ Rome, Dept Med Surg Sci & Biotechnol, Polo Pontino, I-04100 Latina, Italy
[8] IDI IRCCS Ist Dermopat Immacolata, I-00167 Rome, Italy
关键词
head and neck cancer; gene mutation; immunotherapy; cytokines profile; chemokines; soluble immune checkpoints; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER; MUTATIONS; REPAIR; PD-1; LYMPHOCYTES; MECHANISMS; INHIBITION; PHENOTYPE; RECURRENT;
D O I
10.3390/biomedicines10112732
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:25
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