Abstract 6179: Increased circulating PD-L1 expressing CD14 high CD16 negative classical monocytes correlate with poor prognosis in cancer patients treated with PD-1 blockade therapies
Authors: Ohkuma Ryotaro , Ieguchi Katsuaki , Watanabe Makoto , Goshima Tsubasa , Onoue Rie , Hamada Kazuyuki , Kubota Yutaro , Horiike Atsushi , Tsurui Toshiaki , Suzuki Risako , Iriguchi Nana , Ishiguro Tomoyuki , Hirasawa Yuya , Ariizumi Hirotsugu , Yoshimura Kiyoshi , Tsuji Mayumi , Kiuchi Yuji , Kobayashi Shinichi , Tsunoda Takuya , Wada Satoshi 
Published: June 2022

Abstract
Background: Immune checkpoint inhibitors (ICIs), like PD-1 and PD-L1 blockade therapies, are currently considered as one of the most significant breakthroughs in potent cancer immunotherapy. However, many patients are non-responders or develop resistance following an initial response to ICIs. ICIs have no accurate predictive biomarkers. Previously, we showed that increased expression of PD-L1 molecules on CD14+ monocytes was significantly correlated with shorter overall survival (OS) for patients with several cancer types on PD-1 blockade therapies. As monocytes can be further classified into subsets (classical, intermediate, non-classical), we herein investigated the prognostic factors in peripheral blood mononuclear cell (PBMC) subsets and assessed the clinical significance for the PD-L1-expressing subsets of each of these cells including classical, intermediate and non-classical monocyte subsets in patients with various cancer types, along with their clinical implications in PD-1 blockade therapies.
Material and Methods: We evaluated 44 patients (20 with gastric cancer, 17 with non-small cell lung carcinoma, and 7 with esophageal cancer) undergoing PD-L1 blockade therapy (pembrolizumab or nivolumab) for PD-L1 expression levels in classical (CD14high, CD16-), intermediate (CD14high, CD16+), and non-classical (CD14low, CD16+) monocytes measured via flow cytometry before ICI treatment. The percentages of PD-L1+ cells in respective monocyte subsets were compared with respect to different clinicopathological conditions and the association with survival time was assessed.
Results: The number of PD-1 positive cells in CD14+ monocytes was very low (almost &lt;1%). Also, the monocyte subset expressing PD-L1 had a high percentage of classical monocytes, whereas non-classical monocytes expressed less PD-L1. Higher levels of classical monocytes were correlated with shorter OS (P = 0.044), whereas higher levels of non-classical monocytes were correlated with longer OS (P = 0.027). Focusing on non-small cell lung cancer population (N = 17), higher levels of PD-L1-expressing CD14+ monocytes were statistically correlated with shorter OS (P = 0.025). Furthermore, analysis of a subset of monocytes showed that the higher PD-L1-expressing classical monocytes correlated with the shorter OS, suggesting that they predict poor prognosis (P = 0.0095).
Conclusion: Circulating PD-L1-expressing classical monocytes in the peripheral bloods were associated with poor prognosis in patients treated with PD-1 blockade therapies. Among the monocyte subsets, classical monocyte, especially PD-L1-expressing classical monocytes can be a potential biomarker for prognosis in these patients.
Citation Format: Ryotaro Ohkuma, Katsuaki Ieguchi, Makoto Watanabe, Tsubasa Goshima, Rie Onoue, Kazuyuki Hamada, Yutaro Kubota, Atsushi Horiike, Toshiaki Tsurui, Risako Suzuki, Nana Iriguchi, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Kiyoshi Yoshimura, Mayumi Tsuji, Yuji Kiuchi, Shinichi Kobayashi, Takuya Tsunoda, Satoshi Wada. Increased circulating PD-L1 expressing CD14 high CD16 negative classical monocytes correlate with poor prognosis in cancer patients treated with PD-1 blockade therapies [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 6179.