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

Authors
 Seung Hyuck Jeon  ;  Yong Joon Lee  ;  Hyung-Don Kim  ;  Heejin Nam  ;  Baek-Yeol Ryoo  ;  Su-Hyung Park  ;  Changhoon Yoo  ;  Eui-Cheol Shin 
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 (cMonocyte(D7/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-PDL1(D7/D0)) was higher in NDB patients than DCB patients. The combined biomarker cMonocyte(D7/D0)/cMonocyte-PDL1(D7/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.
Files in This Item:
T202302937.pdf Download
DOI
10.1007/s00262-022-03258-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yong Joon(이용준)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195320
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