Abstract 6146: PD1 expression and immune-active lymphocytes can predict recurrence of hepatocellular carcinoma
Authors: Hess Gabriel Fridolin , Coto-Llerena Mairene , Zeindler Jasmin , Däster Silvio , Muenst Simone , Vosbeck Jürg , Ercan Caner , Kollmar Otto , Piscuoglio Salavtore , Soysal Savas Deniz 
Published: June 2022

Abstract
Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Curative treatments in early-stage HCC are hampered by high recurrence rates, and targeted therapies against HCC are rare. Little is known about the impact of tumor microenvironment (TME) in this tumor. Manipulation of the immune system by tumors leads to compromised antigen recognition and an immunosuppressive microenvironment. One immunomodulatory strategy employed by malignant tumors is the expression of the programmed cell death receptor 1 ligand (PD-L1), whose receptor is expressed on activated T cells (PD-1). The use of immune checkpoint inhibitors (ICI) has shown antitumor activity and unprecedented rates of durable clinical responses in various cancer types. In HCC, nivolumab and pembrolizumab are described as possible second line therapies. Expression of PD-1 and PD-L1 in the TME has prognostic importance and can predict response to ICI. The aim of our study was to investigate the impact of PD-1 and PD-L1 expression on HCC recurrence and the relation to their cancer-immune phenotypes.
Materials and methods: Immunohistochemical staining was performed on archival tissue from 91 HCC, primary and recurrence, using the following antibodies: NAT105 (PD-1) and Ventana SP263 (PD-L1). On the basis of protein expression, tumors were classified as immunologically active, excluded or deserted. PD-1 and PD-L1 immunoreactivity was evaluated as the proportion of positive staining of the total number of immune cells (0%, &lt;1% and &gt;1%).
Results: Basic tumor characteristics were not related to recurrence of HCC. However, the immune-excluded subclass showed significant association with recurrence in HCC. The majority of non-recurrent HCC showed PD-1 expression &gt;1% (78%; 38/49), also statistically significant. Conversely, recurrent HCC showed low PD-1 expression (0% or &lt;1%) in 42% (19/45) of the cases. Of note, HCC classified as immune active were enriched for PD-1 positive (&gt;1%) (77%; 49/64). An association between HCC recurrence and PD-L1 expression on tumor cells was not found.
Conclusion: In concordance with previous reports, we found an association between low frequency of PD-1 expression and increased HCC recurrence, as well as the lack of impact of PD-L1 expression on HCC recurrence. Furthermore, our results suggest that HCC recurrence may be more frequent in immune-exclusive tumors. Pembrolizumab as adjuvant instead of 2nd line therapy should be further investigated.
Citation Format: Gabriel Fridolin Hess, Mairene Coto-Llerena, Jasmin Zeindler, Silvio Däster, Simone Muenst, Jürg Vosbeck, Caner Ercan, Otto Kollmar, Salavtore Piscuoglio, Savas Deniz Soysal. PD1 expression and immune-active lymphocytes can predict recurrence of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6146.