PD-L1, fibrosis, and immunotherapy in hepatocellular carcinoma: the importance of a scientific method to explore observa
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LETTER TO THE EDITOR
PD‑L1, fibrosis, and immunotherapy in hepatocellular carcinoma: the importance of a scientific method to explore observations and answer questions Fabio Grizzi1 · Dorina Qehajaj1 · Daniel Yiu2 · Robert S. Bresalier3 · Maurizio Chiriva‑Internati3,4 Received: 24 December 2019 / Accepted: 10 January 2020 © Springer Nature Singapore Pte Ltd. 2020
Keywords PD-L1 · Liver · Cancer · Fibrosis · Immunotherapy Dear Editor, In light of promising data demonstrating a restoration of host immunity against tumors after inhibition, the PD-1/PD-L1 axis has become a topic of particular interest. Determining which patients derive benefit from PD-1/PD-L1-directed immunotherapy remains, however, an important clinical question, particularly in light of the reported broad spectrum of toxicity of these agents. In a recent edition of Surgery Today, Elmezayen et al. [1] reported that PD-L1-expressing cells in the background liver, but not in the tumor tissue, appeared to contribute to the serum PD-L1 (sPDL1) level, suggesting that sPDL1 was not indicative of the tumor burden in patients with hepatocellular carcinoma (HCC). The Authors also observed that: (a) the source of serum PD-L1 might depend on the inflammatory status; (b) the serum PD-L1 does not predict the tissue PD-L1 expression in tumor tissue; and (c) the serum PD-L1 level was not significantly associated with the fibrosis stage but was associated with the tissue PD-L1 status in the background liver. However, they inadequately analyzed the relationships between the PD-L1 expression and the pathological fibrosis or the hepatitis * Fabio Grizzi [email protected] 1
Department of Immunology and Inflammation, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano 20089, Milan, Italy
2
Oxford University Hospitals NHS Foundation Trust, Oxford, UK
3
Division of Internal Medicine, Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer, Houston, TX, USA
4
Kiromic Biopharma, Inc., Houston, TX, USA
activity, which were assessed using methods that were completely different from each other and which were incomparable. The PD-L1 expression was quantified by means of a computer-aided image analysis system and expressed as the PD-L1-positive area, representing PD-L1 expressing cells, irrespective of cell type (i.e. stromal or tumoral cells). In contrast, pathological fibrosis was subjectively determined in the background liver applying the new Inuyama classification [1], which is based on five classes as follows: F0, no fibrosis; F1, fibrosis portal expansion; F2, bridging fibrosis (portal-portal or portal-central linkage); F3, bridging fibrosis with lobular distortion (disorganization); and F4, cirrhosis. The hepatitis activity includes the 4 following categories: A0, no necro-inflammatory reaction; A1, mild necro-inflammatory reaction; A2, moderate necro-inflammatory reaction; and A3, severe necro-inflammatory reaction. The current scoring systems apply the same principles for desc
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