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Title: Functional and Phenotypic Characterization of Tumor-Infiltrating Leukocyte Subsets and Their Contribution to the Pathogenesis of Hepatocellular Carcinoma and Cholangiocarcinoma
Authors: Martín-Sierra, C. 
Martins, R. 
Laranjeira, P. 
Coucelo, M. 
Abrantes, A. M. 
Oliveira, R. C. 
Tralhão, J. G. 
Botelho, M. F. 
Furtado, E.
Domingues, M. R. M. 
Paiva, A. 
Issue Date: Nov-2019
Publisher: Elsevier
Project: European Commission's Horizon 2020 research and innovation program for the Marie Sklodowska-- Curie (grant agreement number 675132) (MSCAITN-ETN MASSTRPLAN) to Centro Hospitalar e Universit ario de Coimbra, Coimbra (Portugal) 
Serial title, monograph or event: Translational Oncology
Volume: 12
Issue: 11
Abstract: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. In the present study, we evaluated the tumor-infiltrating leukocyte (TIL) populations in 21 HCC patients and 8 CCA patients by flow cytometry immediately after the surgical procedure. Moreover, CD4+ T cells, CD8+ T cells, monocytes, and macrophages were purified by cell sorting for further analysis of gene expression by quantitative reverse-transcription polymerase chain reaction. Regarding tumor-infiltrating macrophages, we observed a significantly higher expression of markers associated with M2 phenotype and a higher expression of PD-L1 in patients with HCC in comparison to CCA. In addition, for HCC patients, we found a significant increase in the expression of CD200R in macrophages from tumors that were in grade G3-G4 as compared to tumors in grade G1-G2. Besides, a significantly higher frequency of tumor-infiltrating lymphocytes, CD8+CD56+ T cells, and natural killer cells was detected in HCC biopsies in comparison to CCA. In summary, this study has revealed functional and phenotypic differences in TIL cell subpopulations between CCA and HCC, as well as among different histopathological grades and tumor aggressiveness degrees, and it has provided evidence to better understand the tumor immune microenvironment of CCA and HCC.
ISSN: 1936-5233
DOI: 10.1016/j.tranon.2019.07.019
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais

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