Viral status, immune microenvironment and immunological response to checkpoint inhibitors in hepatocellular carcinoma

Autor: Ludmila Danilova, Elana J. Fertig, Won Jin Ho, Elizabeth M. Jaffee, Rohan X. Verma, Marcelo B. Sztein, James M. Leatherman, Mark Yarchoan, Stephanie Xavier, Hao Wang, Su Jin Lim
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Hepatitis B virus
Cancer Research
Carcinoma
Hepatocellular
Cirrhosis
T-Lymphocytes
T cell
Clinical Decision-Making
Programmed Cell Death 1 Receptor
Immunology
Hepacivirus
B7-H1 Antigen
03 medical and health sciences
Liver disease
Hepatitis B
Chronic
Lymphocytes
Tumor-Infiltrating
0302 clinical medicine
Tumor Microenvironment
medicine
Humans
Immunology and Allergy
Mass cytometry
Antigens
Viral
Immune Checkpoint Inhibitors
B cell
RC254-282
Retrospective Studies
Clinical/Translational Cancer Immunotherapy
Pharmacology
Tumor microenvironment
business.industry
Patient Selection
Liver Neoplasms
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Hepatitis C
Chronic
medicine.disease
meta-analysis
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
Molecular Medicine
liver disease
business
Cytometry
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: Background and aimsImmune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have clinical activity in hepatocellular carcinoma (HCC), but only a subset of patients respond to these therapies, highlighting a need for novel biomarkers to improve clinical benefit. HCC usually occurs in the setting of liver cirrhosis from chronic hepatitis B or C viral infection, but the effects of viral status on the tumor immune microenvironment and clinical responses to ICIs in HCC remains unclear.MethodsWe conducted a meta-analysis to estimate the objective response rates for PD-1/PD-L1 inhibitors in virally-infected and uninfected patients, and examined the effects of viral etiology on the tumor microenvironment using data from The Cancer Genome Atlas, as well as peripheral blood responses using an independent cohort of patients studied by mass cytometry (cytometry by time-of-flight (CyTOF)).ResultsMeta-analysis comparing objective response rates (ORR) between virally-infected and uninfected patients showed no clinically meaningful difference (absolute difference of ORR in virally-infected vs uninfected=−1.4%, 95% CI: −13.5% to 10.6%). There was no relationship between viral etiology on features of the tumor immune microenvironment that are known to modulate responses to PD-1/PD-L1 inhibitors, and the tumor mutational burden was similar between virally-infected and uninfected HCC. RNA sequencing of tissue-resident T cell and B cell repertoires similarly showed no effect of viral status on their diversity. CyTOF analysis of peripheral blood specimens further demonstrated similar expression of immune-related markers in response to PD-1 inhibitor therapy in virally-infected and uninfected HCC.ConclusionThere is no significant effect of viral etiology on the tumor immune microenvironment in HCC, and viral status should not be used as a criterion to select patients for PD-1/PD-L1 therapy.
Databáze: OpenAIRE
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