Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.

Details

Serval ID
serval:BIB_5E664B01B65D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.
Journal
Gastroenterology
Author(s)
Haber P.K., Castet F., Torres-Martin M., Andreu-Oller C., Puigvehí M., Miho M., Radu P., Dufour J.F., Verslype C., Zimpel C., Marquardt J.U., Galle P.R., Vogel A., Bathon M., Meyer T., Labgaa I., Digklia A., Roberts L.R., Mohamed Ali M.A., Mínguez B., Citterio D., Mazzaferro V., Finkelmeier F., Trojan J., Özdirik B., Müller T., Schmelzle M., Bejjani A., Sung M.W., Schwartz M.E., Finn R.S., Thung S., Villanueva A., Sia D., Llovet J.M.
ISSN
1528-0012 (Electronic)
ISSN-L
0016-5085
Publication state
Published
Issued date
01/2023
Peer-reviewed
Oui
Volume
164
Number
1
Pages
72-88.e18
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Single-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1.
Overall, 111 tumor samples from patients with aHCC were obtained from 13 centers before systemic therapies. We performed molecular analysis and immune deconvolution using whole-genome expression data (n = 83), mutational analysis (n = 72), and histologic evaluation with an endpoint of objective response.
Among 83 patients with transcriptomic data, 28 were treated in frontline, whereas 55 patients were treated after tyrosine kinase inhibitors (TKI) either in second or third line. Responders treated in frontline showed upregulated interferon-γ signaling and major histocompatibility complex II-related antigen presentation. We generated an 11-gene signature (IFNAP), capturing these molecular features, which predicts response and survival in patients treated with anti-PD1 in frontline. The signature was validated in a separate cohort of aHCC and >240 patients with other solid cancer types where it also predicted response and survival. Of note, the same signature was unable to predict response in archival tissue of patients treated with frontline TKIs, highlighting the need for fresh biopsies before immunotherapy.
Interferon signaling and major histocompatibility complex-related genes are key molecular features of HCCs responding to anti-PD1. A novel 11-gene signature predicts response in frontline aHCC, but not in patients pretreated with TKIs. These results must be confirmed in prospective studies and highlights the need for biopsies before immunotherapy to identify biomarkers of response.
Keywords
Humans, Carcinoma, Hepatocellular/drug therapy, Carcinoma, Hepatocellular/genetics, Carcinoma, Hepatocellular/metabolism, Liver Neoplasms/drug therapy, Liver Neoplasms/genetics, Liver Neoplasms/metabolism, Programmed Cell Death 1 Receptor/metabolism, Prospective Studies, Biomarkers, Hepatocellular Carcinoma, Immunotherapy, Predictors of Response
Pubmed
Create date
27/09/2022 12:33
Last modification date
28/12/2022 6:52
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