Imperial College London
Alternate

ProfessorRosemaryBoyton

Faculty of Medicine, Department of Infectious Disease

Professor of Immunology and Respiratory Medicine
 
 
 
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Contact

 

r.boyton

 
 
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Location

 

8N22Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pinato:2021:10.1136/jitc-2021-003311,
author = {Pinato, D and Murray, S and Forner, A and Kaneko, T and Fessas, P and Toniutto, P and Minguez, B and Cacciato, V and Avellini, C and Diaz, A and Boyton, R and Altmann, D and Goldin, R and Akarca, A and Marafioti, T and Mauri, F and Casagrande, E and Grillo, F and Giannini, E and Bhoori, S and Mazzaferro, V},
doi = {10.1136/jitc-2021-003311},
journal = {Journal for ImmunoTherapy of Cancer},
pages = {1--9},
title = {Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.},
url = {http://dx.doi.org/10.1136/jitc-2021-003311},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Modulation of adaptive immunity may underscore the efficacy of TACE. We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment.Methods: We profiled intra-tumoural (IT), peri-tumoural (PT) and non-tumoural background tissue (NT) to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163.Results: We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) HCC. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD1+ and NT CD8+/PD1+ (p<0.001) compared to T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed up-regulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-.Conclusions: TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant up-regulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumour microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.
AU  - Pinato,D
AU  - Murray,S
AU  - Forner,A
AU  - Kaneko,T
AU  - Fessas,P
AU  - Toniutto,P
AU  - Minguez,B
AU  - Cacciato,V
AU  - Avellini,C
AU  - Diaz,A
AU  - Boyton,R
AU  - Altmann,D
AU  - Goldin,R
AU  - Akarca,A
AU  - Marafioti,T
AU  - Mauri,F
AU  - Casagrande,E
AU  - Grillo,F
AU  - Giannini,E
AU  - Bhoori,S
AU  - Mazzaferro,V
DO  - 10.1136/jitc-2021-003311
EP  - 9
PY  - 2021///
SN  - 2051-1426
SP  - 1
TI  - Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy.
T2  - Journal for ImmunoTherapy of Cancer
UR  - http://dx.doi.org/10.1136/jitc-2021-003311
UR  - https://jitc.bmj.com/content/9/9/e003311
UR  - http://hdl.handle.net/10044/1/91556
VL  - 9
ER  -
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