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Dynamic changes in peripheral blood monocytes early after anti-PD-1 therapy predict clinical outcomes in hepatocellular carcinoma

Authors
 Bradley J Monk  ;  Takafumi Toita  ;  Xiaohua Wu  ;  Juan C Vázquez Limón  ;  Rafal Tarnawski  ;  Masaki Mandai  ;  Ronnie Shapira-Frommer  ;  Umesh Mahantshetty  ;  Maria Del Pilar Estevez-Diz  ;  Qi Zhou  ;  Sewanti Limaye  ;  Francisco J Ramirez Godinez  ;  Christina Oppermann Kussler  ;  Szilvia Varga  ;  Natalia Valdiviezo  ;  Daisuke Aoki  ;  Manuel Leiva  ;  Jung-Yun Lee  ;  Raymond Sulay  ;  Yulia Kreynina  ;  Wen-Fang Cheng  ;  Felipe Rey  ;  Yi Rong  ;  Guihao Ke  ;  Sophie Wildsmith  ;  Andrew Lloyd  ;  Hannah Dry  ;  Ana Tablante Nunes  ;  Jyoti Mayadev 
Citation
 CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol.72(2) : 371-384, 2023-02 
Journal Title
CANCER IMMUNOLOGY IMMUNOTHERAPY
ISSN
 0340-7004 
Issue Date
2023-02
MeSH
B7-H1 Antigen ; Carcinoma, Hepatocellular* / pathology ; Humans ; Liver Neoplasms* / pathology ; Macrophages ; Monocytes
Keywords
Anti-PD-1 therapy ; Biomarker ; Classical monocyte ; Hepatocellular carcinoma ; Nivolumab
Abstract
Immune checkpoint inhibitors are effective for advanced hepatocellular carcinoma (HCC), but there remains a need for peripheral blood biomarkers to predict the clinical response. Here, we analyzed the peripheral blood of 45 patients with advanced HCC who underwent nivolumab. During treatment, frequency of classical monocytes (CD14+CD16−) was increased on day 7, and the fold increase in the frequency on day 7 over day 0 (cMonocyteD7/D0) was significantly higher in patients with durable clinical benefit (DCB) than in patients with non-DCB (NDB). When we analyzed transcriptomes of classical monocytes, CD274, gene encoding PD-L1, was upregulated in NDB patients compared to DCB patients at day 7. Notably, gene signature of suppressive tumor-associated macrophages, or IL4l1+PD-L1+IDO1+ macrophages, was enriched after treatment in NDB patients, but not in DCB patients. Accordingly, the fold increase in the frequency of PD-L1+ classical monocytes at day 7 over day 0 (cMonocyte-PDL1D7/D0) was higher in NDB patients than DCB patients. The combined biomarker cMonocyteD7/D0/cMonocyte-PDL1D7/D0 was termed the “monocyte index”, which was significantly higher in DCB patients than NDB patients. Moreover, the monocyte index was an independent prognostic factor for survival. Overall, our results suggest that early changes of circulating classical monocytes, represented as a monocyte index, could predict clinical outcomes of advanced HCC patients undergoing anti-PD-1 therapy. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Files in This Item:
T999202467.pdf Download
DOI
10.1007/s00262-022-03258-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yong Joon(이용준)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198267
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