RFA-INDUCED ALTERATIONS IN THE EXPRESSION OF PD-1 AND CTLA-4 IN THE TUMOUR MICROENVIRONMENT pCCA: RESULTS FROM AN EXPLORATORY STUDY
BIANCA GĂLĂȚEANU 1#, OCTAV GINGHINĂ 2,3#, ARIANA HUDIȚĂ 1,4*, RALUCA-SILVANA TUDORACHE 5, MARIUS-COSMIN ZAMFIR 3,6, MARA MARDARE 3,6, CLAUDE LAMBERT 7, MIHAELA BÎRLIGEA 8,9, CLAUDIA DIACONU 8, CRISTIANA POPP 8,9, GEORGE-TRAIAN- ALEXANDRU BURCEA-DRAGOMIROIU 10, ANDREI VOIOSU 8,9, THEODOR VOIOSU 8,9
1Faculty of Biology, University of Bucharest, Bucharest, Romania
2Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3Department of Surgery 3, “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, Romania
4Research Institute of the University of Bucharest, University of Bucharest, Bucharest, Romania
5The University of York, York, United Kingdom
6Doctoral School of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
7Central University Hospital Saint-Etienne, Saint-Etienne, France
8Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania
9Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
10Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
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Cholangiocarcinoma (CCA) is a rare form of cancer, accounting for approximately 3% of all gastrointestinal cancers and 15% of primary liver malignancies. Most patients will require a multidisciplinary approach, including palliative, radiotherapy and systemic therapy (chemotherapy or, more recently, immunotherapy). Local ablation therapy using radiofrequency ablation (RFA) has also been explored in the setting of perihiliar cholangiocarcinoma (pCCA) as an adjunctive to palliative drainage. Tumour-infiltrating lymphocytes (TILs) are an adaptive immune cell type that can travel directly to the tumoural site to suppress cancer proliferation and development. Immune checkpoint inhibitor (ICI)-based therapies that act directly on the T-cell signalling pathway have proven particularly useful in recent trials, with molecules targeting the cytotoxic T-lymphocytes associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways showing efficacy in a wide range of indications. In this context, our study aimed to measure the potential effect of RFA on the intratumoural expression of checkpoint molecules, with an impact on modulating immunotherapy. We present here an exploratory study presenting an optimized flow cytometry protocol for tissue dissociation and cell characterization in terms of PD-1/PD-L1 and CTLA-4 expression. Our results show that RFA significantly increases the infiltration of cluster of differentiation 8+ (CD8+) cells and that the expression of PD-1 and CTLA-4 was significantly increased on cluster of differentiation 3+ (CD3+) cells after RFA. RFA might promote a “switch” from an “immune-cold” to an “immune-hot” tumour microenvironment (TME) profile, with a significant impact on enabling immunotherapy for CCA patients.