Abstract 126P
Background
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and its incidence is steadily rising. Recently, immune-checkpoint inhibitors have revolutionized the management of HCC and combination of atezolizumab and bevacizumab has been shown to improve overall survival. We performed a molecular and cellular characterization of the tumour microenvironment that plays a crucial role in the development of HCC.
Methods
We performed a sequential treatment with anti-PD-L1 atezolizumab in combination with anti-VEGF bevacizumab for 6 days followed by tyrosine kinase inhibitor (TKI) lenvatinib for additional 6 days on HCC cell lines (HuH7 and SNU449) and then we measured the resulted effect by MTT assay for cell proliferation. After treatments we investigated tumour microenvironment (vimentin, cadherin) and immune markers (PD-L1, CTLA4 and cytokines) on HuH7 and SNU449 cells co-coltured with PBMCs (peripheral blood mononuclear cells) through RT-PCR.
Results
Combination of atezolizumab and bevacizumab followed by lenvatinib shows a reduction of cell growth, we observed a decrease in cell proliferation of 53.2 and 58.1 % for HuH7 and SNU449 respectively. This result is enhanced in cell co-coltures with PBMCs, in which cell viability is significantly reduced reaching value of 37.5 and 38.2 % for HuH7 and SNU449. We observed a decrease of PD-L1 and CTLA4 and a parallel increase of IFNγ, GRZb, IL-6 and IL1β, all cytokines able to create favourable microenvironment for inflammatory and immune response. The effect is accompanied by a functional change in favour of EMT blockade with increased cadherin and reduced vimentin expression (8.26- and 0.5-fold increase values, for cadherin and vimentin respectively, compared to untreated control) after sequential treatments.
Conclusions
Our work could provide good perspectives on predictability and sensitivity to new drug combination strategies in patients with HCC resistant to immune blockade. We aim to confirm the effect of the treatment also in ex vivo human spheroids and patients derived lymphocytes co-coltures, to verify the possible synergism of PD-L1 and VEGF inhibition on cytokine secretion profile.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
62P - Role of IL6 (C-174G) polymorphism in the development of cervical intraepithelial neoplasia
Presenter: Tatyana Abakumova
Session: Cocktail & Poster Display session
Resources:
Abstract
63P - The impact of disruption of melatonin secretion on the structural-functional changes of the microbiome and the role of the melatonin-microbiome axis in the initiation of carcinogenesis
Presenter: Alexandre Tavartkiladze
Session: Cocktail & Poster Display session
Resources:
Abstract
64P - Acidosis induces ferroptosis of breast cancer via ZFAND5/SLC3A2 axis with the synergistic effect of metformin and facilitates M1 macrophage polarization
Presenter: Hanchu Xiong
Session: Cocktail & Poster Display session
Resources:
Abstract
65P - Transmembrane distribution of phosphatidylethanolamine in plasma membrane of ovarian cancer cells under conditions mimicking tumor microenvironment
Presenter: Darya Savenkova
Session: Cocktail & Poster Display session
Resources:
Abstract
66P - Metabolic regulation of GMP- and MDP-derived macrophages in glioblastoma
Presenter: Liam Wilson
Session: Cocktail & Poster Display session
Resources:
Abstract
67P - Inflammation status and sarcopenia synergistically impact outcomes in cancer patients (pt) treated with ImmunOtherapy (IO) within the framework of a Molecular Pre-screening program (MP) and a spEcial Medication (ME) program
Presenter: Lucia Notario Rincon
Session: Cocktail & Poster Display session
Resources:
Abstract
68P - The role of systemic reprogramming of GMPs in improving outcomes in glioblastoma
Presenter: Aline Atallah
Session: Cocktail & Poster Display session
Resources:
Abstract
69P - Integrated OMIC analysis reveals arginine and proline metabolism plays critical role in hypoxia-induced oral squamous cell carcinoma
Presenter: Avinash Singh
Session: Cocktail & Poster Display session
Resources:
Abstract
70P - Individualising methotrexate dose based on MTHFR gene polymorphisms in acute lymphoblastic leukemia
Presenter: Meher Konatam
Session: Cocktail & Poster Display session
Resources:
Abstract
71P - Single nucleotide polymorphisms in the folate metabolic pathway genes and global DNA methylation in ovarian cancer
Presenter: Sandro Surmava
Session: Cocktail & Poster Display session
Resources:
Abstract